The efficacy of sclerotherapy as the initial treatment in patients with bleeding from Dieulafoy's lesion of the upper gastrointestinal tract.

BACKGROUND: Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL). METHODS: Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist. RESULTS: In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30 days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0 days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5 days, p = 0.005) compared to sclerotherapy alone. CONCLUSION: Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL.

Nomogram for predicting electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) was widely used for the removal of esophageal tumors, and post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was one of the postoperative adverse events. The aim of this research was to develop and validate a model to predict electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors. MATERIALS AND METHODS: Patients who underwent esophageal ESD in our hospital were retrospectively included. A predictive nomogram was established based on the results of multivariate logistic regression analysis, and bootstrapping resampling was used for internal validation. Besides, the clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA) and clinical impact curve. RESULTS: A total of 552 patients who underwent esophageal ESD were included in the study, and the incidence of PPECS was 12.5% (69/552). Risk factors associated with PEECS (p < 0.1) were analyzed by multivariate logistic regression analysis, and the final model included four variables, namely gender, diabetes, tumor size and operation time. The predictive nomogram was constructed based on the above four variables, and the area under the ROC curve (AUC) was 0.811 (95% CI 0.767-0.855). The calibration curve of the nomogram presented good agreement between the predicted and actual probabilities. DCA showed that the model improved patient outcomes by helping to assess the risk of PEECS in patients compared to an all-or-no treatment strategy. In addition, the clinical impact curve of the model also indicates that the nomogram has a high clinical net benefit. CONCLUSION: In conclusion, we have developed a predictive nomogram for PEECS after ESD for esophageal tumors with good predictive accuracy and discrimination. This predictive nomogram can be effectively used to identify high-risk patients with PEECS, which will help clinicians in clinical decision-making and early intervention.

Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route.

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.

Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers).

BACKGROUND: Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. METHODS: We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. RESULTS: A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). CONCLUSIONS: Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.

Controlled synthesis of α-Fe2O3 nanocubes for gas-sensing applications: Feasibility of assessing crucian carp (Carassius auratus) freshness via trimethylamine levels.

Trimethylamine (TMA) is an organic amine with strong pungent smell which is an indicator gas for evaluating fish freshness according to the international standard. In this work, as-synthesize α-Fe2O3 solid nanocubes (NCs), α-Fe2O3 nucleoshell NCs and α-Fe2O3 hollow NCs were used as sensing material to develop an outstanding TMA gas sensor. The response of the α-Fe2O3 hollow NCs sensors towards 20 ppm TMA at 230 ℃ was 6.3. Meanwhile, these sensors showed exceptional response/recovery time, low limit of detection, great selectivity, and outstanding linear relationship. Furthermore, the analysis of gases released during the decomposition of Carassius auratus (0-10 days) was conducted, which demonstrated the assessment of TMA by α-Fe2O3 hollow NCs sensor can evaluate the freshness of Carassius auratus. Such a novel sensor signifies the outstanding application potential in efficient gas-sensing properties of TMA, which will make the tremendous contribution for Carassius auratus product evaluation in the future.

Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

First record of the genus Camptotheca (Nyssaceae) in Vietnam and the lectotypification of C.acuminata.

As a primary source of anticancer camptothecin, Camptotheca (Nyssaceae) is an economically valuable genus and has long been recorded as endemic to China. Here, Camptotheca is reported as a new record to the flora of Vietnam with the discovery of a wild population of C.acuminata from Lai Chau Province of northern Vietnam. Based on the consultation of relevant literature and type specimens of C.acuminata, a lectotype of the species is designated. Photographic illustrations, morphological description and a distribution map of C.acuminata is provided, and a key to all known species of Nyssaceae in Vietnam is presented, too.

Investigation of the prevalence and risk factors of Helicobacter pylori infection and the value of different gastric cancer screening methods in a low-risk region of gastric cancer in China.

BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.

Recent advances in mucus-penetrating nanomedicines for oral treatment of colonic diseases.

INTRODUCTION: Oral administration is the most common route for treating colonic diseases that present increased incidences in recent years. Colonic mucus is a critical rate-limiting barrier for the accumulation of oral therapeutics in the colonic tissues. To overcome this obstacle, mucus-penetrating nanotherapeutics have been exploited to increase the accumulated amounts of drugs in the diseased sites and improve their treatment outcomes against colonic diseases. AREAS COVERED: In this review, we introduce the structure and composition of colonic mucus as well as its impact on the bioavailability of oral drugs. We also introduce various technologies used in the construction of mucus-penetrating nanomedicines (e.g. surface modification of polymers, physical means and biological strategies) and discuss their mechanisms and potential techniques for improving mucus penetration of nanotherapeutics. EXPERT OPINION: The mucus barrier is often overlooked in oral drug delivery. The weak mucus permeability of conventional medications greatly lowers drug bioavailability. This challenge can be addressed through physical, chemical and biological technologies. In addition to the reported methods, promising approaches may be discovered through interdisciplinary research that further helps enhance the mucus penetration of nanomedicines.

Treatment of Anterior Dislocation of the Sacroiliac Joint via the Lateral-rectus Approach: Surgical Techniques and Preliminary Outcomes.

OBJECTIVE: Anterior dislocation of the sacroiliac joint (ADSIJ) is caused by strong violence, and because of its low morbidity, there are no standardized diagnostic and therapeutical guidelines at this moment. This study aims to explore the surgical techniques and preliminary outcomes of the lateral-rectus approach (LRA) for treating ADSIJ. METHODS: A retrospective study was conducted of 15 patients with ADSIJ from January 2016 to January 2021. The patients' age ranged from 1.8 years old to 57 years old (37 ± 18 years old). All patients underwent open reduction and internal fixation (ORIF) through the LRA. Eight patients were combined with lumbosacral plexus injury and underwent neurolysis during operation. Patients' fracture type, mechanism of injury, associated injuries, operation time and intraoperative bleeding volume were accessed by reviewing medical history. Quality of fracture reduction was evaluated with the Matta score. At 1-year follow-up, the functional rehabilitation was evaluated by the Majeed rehabilitation criteria. For those with lumbosacral plexus injury, the neuromotor function was evaluated using muscle strength grading proposed by the British Medical Research Council (BMRC) and recovery was recorded. RESULTS: All 15 patients underwent the operation successfully. The surgical time ranged from 70 to 220 min (126 ± 42 min), and the intraoperative blood loss ranged from 180 to 2000 mL (816 ± 560 mL). Eighty percent of the cohort (12/15) were rated as excellent and good in the Matta score for fracture reduction quality after operation without surgical incision-related complications. At 1-year follow-up, the overall excellent and good rate was 73.3% (11/15) according to the Majeed criteria, the neuromotor function recovered completely in six cases and partially in two cases according to the BMRC muscle strength grading, and the recovery of sensory function was evaluated as excellent in six cases, good in one case and poor in one case, with an overall excellent and good rate of 87.5%. CONCLUSION: The LRA can well expose the surrounding structures of the sacroiliac joint from the front, which helps surgeons reduce and fix the anterior dislocation of the sacroiliac joint under direct vision and effectively decompress the entrapment of the lumbosacral plexus to achieve better clinical efficacy.

Expression, regulating mechanism and therapeutic target of KIF20A in multiple cancer.

Kinesin family member 20A (KIF20A) is a member of the kinesin family. It transports chromosomes during mitosis, plays a key role in cell division. Recently, studies proved that KIF20A was highly expressed in cancer. High expression of KIF20A was correlated with poor overall survival (OS). In this review, we summarized all the cancer that highly expressed KIF20A, described the role of KIF20A in cancer. We also organized phase I and phase II clinical trials of KIF20A peptides vaccine. All results indicated that KIF20A was a promising therapeutic target for multiple cancer.

Posterior wall fractures of the acetabulum: treatment using an anatomical plate through direct posterior approach.

OBJECTIVES: This study was aimed to measure the application of W-shaped acetabular angular plate (WAAP) through direct posterior approach (DPA) on the reconstruction of acetabular posterior wall fractures when compared with reconstruction plates. PATIENTS AND METHODS: A retrospective study was performed on patients treated with the WAAP or reconstruction plates via the DPA. The intraoperative data of operative time, blood loss and radiation exposure times were recorded. Radiographs of the pelvis and CT scan were obtained within one week post-operation to assess the reduction quality. The clinical outcome was evaluated by the modified Merle d'Aubigne and Postel score. RESULTS: From May 2016 to October 2019, a total of 41 patients with simple acetabular posterior wall fractures were included in this study, 22 from the WAAP group and 19 from the reconstruction plates group. There were no significant differences between the two group in age, gender, time from injury to operation, cause of injuries, length of incision and follow-up time (P > 0.05). In comparison with the reconstruction plates group, the average operation time of the WAAP group was significantly shorter (46.1 ± 12.7 min vs 59.2 ± 17.4 min, P < 0.05), the average radiation exposure times were significantly less (2.3 ± 0.6 vs 3.6 ± 1.0, P < 0.001), the average blood loss was significantly less (240 ± 98.9 ml vs 301.1 ± 66.6 ml, P < 0.05). According to Matta radiology criteria and the modified Merle d' Aubigne and Postel score, no significant difference was observed between the two group, as for the quality of reduction and function outcomes. CONCLUSION: The application of WAAP through DPA showed satisfactory preliminary clinical outcomes, showing promise to be an alternative technique for the treatment of acetabular posterior wall fractures.

Routine nasogastric tube placement after gastric endoscopic full-thickness resection of tumor size ≤ 2 cm may be unnecessary: a propensity score-matching analysis.

BACKGROUND: Endoscopic full-thickness resection is a common endoscopic procedure for treating gastrointestinal submucosal tumors. Nasogastric tube placement is frequently performed after abdominal surgery, but the routine use of this approach remains controversial. The aim of this research was to explore whether nasogastric tube placement after gastric endoscopic full-thickness resection is necessary. METHODS: A retrospective study enrolled patients who underwent gastric endoscopic full-thickness resection in our hospital between January 2014 and January 2019, and all the patients had a tumor size ≤ 2 cm. The patients were divided into two groups according to whether a nasogastric tube was placed. Postprocedural adverse events and hospital stay duration were compared between the two groups using 1:1 propensity score matching. RESULTS: A total of 461 patients were enrolled in this study, including 385 patients in the nasogastric tube group (NGT group) and 76 patients in the non-nasogastric tube group (non-NGT group). After matching, the baseline characteristics of 73 patients in the NGT group and 73 patients in the non-NGT group were balanced (p > 0.05). The postprocedural fever rate in the NGT group was significantly higher than that in the non-NGT group (23.3% vs. 9.6%, p = 0.044). 6.9% (5/73) of patients experienced severe nasogastric tube-related throat discomfort. However, the duration of hospitalization stay was not different between the two groups. CONCLUSIONS: For patients with tumor size ≤ 2 cm, routine nasogastric tube placement after gastric endoscopic full-thickness resection may be unnecessary.

Mucus-Penetrating Silk Fibroin-Based Nanotherapeutics for Efficient Treatment of Ulcerative Colitis.

Oral nanoparticles have been considered a prospective drug delivery carrier against ulcerative colitis (UC). To enhance the mucus-penetrating capacity and aqueous solubility, and strengthen the anti-inflammatory effect of resveratrol (RSV), we fabricated RSV-loaded silk fibroin-based nanoparticles with the functionalization of Pluronic F127 (PF-127). The obtained PF-127-functionalized RSV-loaded NPs had an average particle size around 170 nm, a narrow size distribution (polydispersity index < 0.2), and negative zeta potential (−20.5 mV). Our results indicated that the introduction of PF-127 strengthened the mucus-penetrating property of NPs. In vitro studies suggested that NPs with PF-127 enhanced the suppression of the secretion of proinflammatory cytokine TNF-α and reactive oxygen species (ROS) from RAW 264.7 macrophages under lipopolysaccharide stimulation in comparison with other counterparts. According to the evaluation of macro symptoms and main inflammatory cytokines, we further report preferable therapeutic outcomes achieved by PF-127 functionalized-NP-treated dextran sulphate sodium (DSS) groups in the colitis model compared with blank silk fibroin NPs and RSV-loaded NPs without the functionalization of PF-127. Taken together, this work suggests that the fabricated PF-127 NPs via the oral route are promising and useful RSV-loaded nanocarriers for UC treatment.

Risk Factors for Avascular Necrosis After Closed Reduction for Developmental Dysplasia of the Hip.

BACKGROUND: Avascular necrosis (AVN) is a major complication after closed reduction for developmental dysplasia of the hip. The factors that predispose to AVN remain controversial. The purpose of this study was to analyze the risk factors, especially patient factors, such as age at reduction, grade of dislocation, and ossific nucleus development, related to AVN. MATERIALS AND METHODS: We retrospectively reviewed children with dysplasia of the hip treated by closed reduction between 1997 and 2006. AVN was evaluated using Salter criteria and Kalamchi and MacEwen classification. Related factors were analyzed. RESULTS: One hundred and eight children (140 hips) with an average age of 16.6 months at closed reduction (range: 6-24 mo) were included in the study. For an average duration of 10.1 years (range 7-16 y) of follow-up, 44 hips (31.4%) developed AVN. Grade II or higher AVN occurred in 14 hips (10%). The incidence of AVN increased with the grade of dislocation ( P =0.022) and underdevelopment of the ossific nucleus ( P <0.001). Underdevelopment of the ossific nucleus was also found to be positively correlated with the dislocation grade ( P =0.047). The age at the time of reduction, sex, and side were not significant factors. Children who underwent secondary operation were all older than 1 year at reduction. CONCLUSIONS: High-grade dislocation correlates with the underdevelopment of the ossific nucleus. Patients with these 2 characteristics are predisposed to AVN. As underdevelopment of the ossific nucleus occurred regardless of age, it is not advisable to delay reduction because it does not alter the AVN rate, and instead, it increases the secondary operation rate. LEVEL OF EVIDENCE: Level IV case series.

KIF20A promotes the development of fibrosarcoma via PI3K-Akt signaling pathway.

Adult fibrosarcoma is an aggressive subtype of soft tissue sarcoma (STS), in which high expression of KIF20A indicates a poor prognosis. However, the precise role of KIF20A in fibrosarcoma progression remains unknown. In this study, we initially examined KIF20A expression and function in the human fibrosarcoma cell line HT-1080. The results showed that KIF20A was highly expressed in HT-1080, knockdown of KIF20A impaired cell proliferation, migration, invasion and induced G2/M arrest and cell apoptosis. Transcriptome study suggested that PI3K-Akt signal pathway was involved in these biological changes. We confirmed that PI3K-Akt and NF-κB signaling pathways were impaired after the down-regulation of KIF20A, which can be reversed by the Akt activator SC79 in HT-1080 in vitro. In a xenograft mouse model, knockdown of KIF20A inhibited tumor growth, Ki67 expression and liver metastasis. Taken together, our results suggested that KIF20A promoted fibrosarcoma progression via PI3K-Akt signaling pathway and might be a potential therapeutic target for fibrosarcoma.

The role of TRIM59 in immunity and immune-related diseases.

TRIM59 is a member of the tripartite motif containing (TRIM) protein family. It functions as an E3 ubiquitin ligase through its RING domain and is expressed by multiple types of cells. Physiogically, TRIM59 is involved in development, immune response, and the invasion and metastasis of tumors. In this review, we first describe the structure, expression, and subcellular location of TRIM59. Then, we summarize emerging evidence for TRIM59 in immunological diseases including infection, vascular diseases, autoimmunity, and tumor immunity. Additionally, we discuss important molecular signaling pathways that mediate TRIM59 activity. Altogether, the accumulating evidence suggests that manipulating TRIM59 levels and activity may open an avenue for innovative therapies for immune diseases and tumors.

The immune system plays an important role in maintaining physiology. When immune system is in disorder, there are a series of diseases such as allergy, immune deficiency diseases and persistent infections. Immune system is composed of a large number of immune cells, which plays a major role in fighting bacteria, viruses, parasites fungi, or cancer cells. There are many molecules involved in the regulation of immune balance, including TRIM59. Like other TRIM proteins, TRIM59 is important in tumor invasion and metastasis, immune response and thus pathogenesis of various immune diseases. In this study, we summarized the structure and expression regulation of TRIM59, expounded its effect and mechanism on immunity and immune-related diseases, and discussed the possibility of TRIM59 as a therapeutic target.

Identification of an immune-related gene pair signature in breast cancer.

Background: Although breast cancer outcome has improved significantly with the recent use of molecularly targeted agents, reliable prognostic signatures are still unavailable because of tumor heterogeneity. Immune processes play an important role in tumor progression. Therefore, the aim of this study was to construct a prognostic signature based on immune-related genes (IRGs). Methods: Clinical information and gene expression of 3,496 patients were extracted from eight public data sets. A total of 2,498 IRGs associated to 17 immune processes were downloaded from the ImmPort database. RNA sequencing (RNAseq) datasets [The Cancer Genome Atlas (TCGA) and GSE96058] were used as the training set (n=2,736) and all microarray datasets were used as validation set (n=760). IRGs related to prognosis were screened out from the training set and used to construct gene pairs. The Cox regression model was used, based on the immune-related gene pairs (IRGPs). The risk score of each patient was calculated and patients were stratified into high- and low-risk groups according to the optimal threshold of the risk score. Immune cell infiltration was evaluated between both groups. Results: Among the 129 prognostic-related immune genes, 8,256 IRGPs were constructed. After screening, 89 IRGPs, including 86 unique IRGs, were used in the prognostic prediction model. Patients in the high-risk group exhibited a significantly poorer overall survival (OS) both in the training set [hazard ratio (HR): 5.9, 95% confidence interval (CI): 4.61-7.54] and validation set (HR: 1.52, 95% CI: 1.16-1.98) compared to the low-risk group. In addition, patients in the high-risk group showed a significantly lower infiltration of CD8+ T cells than patients in the low-risk group. Conclusions: An independent IRGP signature was constructed. Through pairwise comparison of a set of genes, the OS of patients could be predicted. This method avoids the impact of the batch effect caused by different sequencing platforms and has a promising application prospect.

Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis.

BACKGROUND: A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear. METHODS: We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured. RESULTS: Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG. CONCLUSION: Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF.

Efficacy of two different types of island flaps for the repair of diabetic foot ulcers on the heel.

Background: Heel ulcer of diabetic foot (DF) is a difficulty in clinical repair. The current study aimed to investigate the clinical efficacy of the medial plantar island flap (MPIF) and the sural nerve nutritional artery island flap (SNNAIF) for the repair of chronic diabetic foot ulcers (DFU) on the heel. Methods: Twelve patients with chronic DFU on the heel were admitted to our department from August 2018 to August 2020. Upon admission, ulcer debridement and bone cement filling were performed for 2-3 weeks to control infection. Digital subtraction angiography (DSA) or computed tomography angiography (CTA) of the lower limb was performed to assess vascular status. Then, 5 patients were repaired with MPIF and 7 patients with SNNAIF. Results: The MPIF survived completely in 5 cases; SNNAIF was used in 7 cases, and 6 cases survived completely. Meanwhile, 1 patient who underwent SNNAIF presented with partial necrosis of the distal end of the flap. Then, it healed after debridement and dressing changes. All 12 flaps were followed up for 6-12 months. The flaps had a soft texture, and their shape was satisfactory. In 2 cases, SNNAIFs re-ruptured 8 months after surgery. However, they healed after dressing changes and weight-bearing reduction. During the 10-month follow-up, the sensory recovery of MPIF in 5 cases was satisfactory because the flap contained medial plantar cutaneous nerve. Meanwhile, 7 patients who underwent SNNAIF repair had poor sensory recovery. All patients had good dorsiflexion and plantarflexion of the ankle with satisfactory function. Conclusions: Both the MPIF and SNNAIF flaps had a high survival rate and are feasible for DFU repair with good clinical outcomes. If DSA or CTA shows that the medial plantar artery is unobstructed and the heel wound is small, MPIF can retain sensory function and wear resistance. It is the first choice for repairing diabetic foot ulcers on the heel. If the heel wound are large or DSA or CTA shows that the posterior tibial artery is occluded and the peroneal artery is unobstructed, SNNAIF repair is safer.