Nonsurgical risk factors for marginal ulcer following Roux-en-Y gastric bypass for obesity: a systematic review and meta-analysis of 14 cohort studies.

BACKGROUNDS: Marginal ulcer (MU) is a common complication of Roux-en-Y Gastric Bypass (RYGB). The primary goal of this meta-analysis was to identify potential risk factors for MU post-RYGB. METHODS: A comprehensive literature search was conducted on four databases (PubMed, Embase, Web of Science, and the Cochrane Library) to identify articles published from inception to 23 May 2023 that reported risk factors linked to ulcer occurrence post-RYGB. Hazard Ratio (HR) and Odds Ratio (OR) with respective 95% CI were calculated to estimate the impact of selected risk factors on MU. The risk factors were evaluated through multivariate analyses. The estimated risk factors were subjected to a random-effects model. Subgroup analysis based on study baseline characteristics and leave-one-out sensitivity analysis were also performed to investigate the potential sources of heterogeneity and assess the robustness of the findings. RESULT: Herein, 14 observational studies involving 77 250 patients were included. Diabetes, smoking, and steroid use were identified to be risk factors of MU, with pooled ORs of (1.812; 95% CI: 1.226-2.676; P =0.003), (3.491; 95% CI: 2.204-5.531; P< 0.001), and (2.804; 95% CI: 1.383-5.685; P =0.004), respectively. Other risk factors, such as alcohol consumption, male sex, and PPI use, were deemed not significant due to differences in data acquisition and effect estimates. CONCLUSION: Diabetes, smoking, and steroid use were identified as independent risk factors of MU. Enhancing awareness of these identified risk factors will lead to more effective preoperative prevention and targeted postoperative interventions for patients undergoing RYGB.

Recurrent hematuria involving urinary system with Klippel-Trenaunay syndrome: A case report.

RATIONALE: Klippel-Trenaunay syndrome (KTS) is a rare congenital venous malformation, it had been found to be caused by mutations of the phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Currently KTS is defined as a triad of skin wine pigmented spots, varicose veins and malformations of the lower extremities, and hypertrophy of bone and soft tissue, involving urinary system up to 6% to 30%. When the urinary system is involved, KTS is often presented as painless massive gross hematuria. PATIENT CONCERNS: This article describes a woman who was hospitalized with painless massive gross hematuria. Physical examination revealed significant hypertrophy of the right lower limb with varicose veins, port-wine stains in the skin, and right perineal hemangiomatous changes with swelling. The patient was admitted to hospital 4 times for repeated hematuria and infection. DIAGNOSES: By physical examination, CT urography, ureteroscopy and cystoscopy, the patient was diagnosed to have Klippel-Trenaunay syndrome, involving the urinary system. INTERVENTIONS: The patient hematuria improved after multiple indwelling D-J tubes and anti-inflammatory treatment. OUTCOMES: The final symptoms of hematuria improved significantly, follow-up so far has not recurred. LESSONS: This case presents the possibility of painless gross hematuria with KTS. Most of patients can be improved by conservative treatment. Cystoscopic laser therapy is the preferred treatment for poor bleeding control. Cystectomy and nephrectomy should be considered when life-threatening.

Comprehensive analysis the diagnosis, malignant progression and immune infiltrate of ANXA6 in prostate cancer.

BACKGROUND: Annexins (ANXAs) play a crucial role in the development and progression of tumors. However, their specific involvement in prostate cancer (PCa) remains unclear. OBJECTIVE: To investigate the function and clinical significance of key ANXAs in PCa. METHODS: Multiple databases were used to analyze the expression levels, genetic variations, potential prognostic value and clinical significance of ANXAs in PCa. Then, the co-expressed genes of ANXA6 were identified, and the correlation between ANXA6 and immune cell infiltration was validated using the Tumor Immune Estimation Resource (TIMER) database. Additionally, in vitro assays such as Cell Counting Kit-8 (CCK-8), Colony Formation, Transwell and T-cell Chemotaxis assays were conducted to validate the functions of ANXA6. Moreover, multiple types of in vivo assays were performed to further validate the identified ANXA6 functions. RESULTS: The results demonstrated that ANXA2, ANXA6 and ANXA8 were significantly downregulated in PCa. ANXA6 upregulation was significantly associated with improved PCa patients' overall survival. Enrichment analysis revealed that ANXA6 and its co-expressed genes were involved in tumor progression, and ANXA6 overexpression could effectively inhibit the proliferation, migration and invasion of PC-3 cells. In vivo studies also demonstrated that ANXA6 overexpression suppressed tumor growth. Importantly, ANXA6 was found to promote the chemotaxis of CD4+ T cells and CD8+ T cells towards PC-3 cells, and the overexpression of ANXA6 in PC-3 cells promoted the polarization of macrophages into M1 macrophages in the supernatant of PCa cells. CONCLUSIONS: ANXA6 demonstrated promising potential for consideration as a prognostic biomarker in PCa as it was found to play key roles in regulating immune cell infiltration and the malignant progression to PCa.

An attack-defense game model in infrastructure networks under link hiding.

Our increasing dependence on infrastructure networks leads to growing concerns over the protection of these networks. Many methods have been proposed to select protective strategies by combining complex network theory and game theory. However, the misleading effect of hidden links is not considered in previous methods. This work creates an information gap between attackers and defenders by partly hiding network links to mislead the attacker in the game. We first introduce the rule of link hiding that depends on the nodes' property, where the number of hidden links has a maximum value. Additionally, based on the Stackelberg game model, we establish an attack-defense game model with link hiding strategies considering node property and cost constraints. Finally, we conduct experiments in a scale-free network and an existing power grid. The experimental results show that the defender tends to combine first-mover advantage and link hiding to get a better payoff under more different costs of the nodes. Hiding half of the links in the existing power grid can effectively reduce network damage by about 22.8% on average, with the two sides investing the same resources. The effect of link hiding could be more obvious when the attacker owns more resources than the defender. When an attacker employs the high-degree attacking strategy, the proposed link hiding method can help the defender reduce the damage to the network by 12.2% compared to the link reconnecting method.

Attack-Defense Game Model with Multi-Type Attackers Considering Information Dilemma.

Today, people rely heavily on infrastructure networks. Attacks on infrastructure networks can lead to significant property damage and production stagnation. The game theory provides a suitable theoretical framework for solving the problem of infrastructure protection. Existing models consider only the beneficial effects that the defender obtains from information gaps. If the attacker's countermeasures are ignored, the defender will become passive. Herein, we consider that a proficient attacker with a probability in the game can fill information gaps in the network. First, we introduce the link-hiding rule and the information dilemma. Second, based on the Bayesian static game model, we establish an attack-defense game model with multiple types of attackers. In the game model, we consider resource-consistent and different types of distributions of the attacker. Then, we introduce the solution method of our model by combining the Harsanyi transformation and the bi-matrix game. Finally, we conduct experiments using a scale-free network. The result shows that the defender can be benefited by hiding some links when facing a normal attacker or by estimating the distribution of the attacker correctly. The defender will experience a loss if it ignores the proficient attacker or misestimates the distribution.

The Prognosis and Immune Microenvironment Related Factor Interleukin-23 in Clear Cell Renal Cell Carcinoma: A Radiological Investigation.

PURPOSE: To explore the ccRCC clinical and immune characteristics correlated with IL-23 expression level and build pre-operative prediction models based on contrast CT scans. MATERIALS AND METHODS: The study included the cancer genome atlas kidney renal clear cell carcinoma cases to build a bioinformatics cohort. The cases with qualified contrast CT images were selected as radiographic and radiomics cohort. The IL-23 expression level groups were defined by median-based thresholding. The clinical characteristics were compared between groups. The impacts of IL-23 on immune microenvironment composition were measured via the CIBERSORT. Two radiologists evaluated the pre-operative contrast CT images. The radiomics features were automatically extracted. IL-23 group-specific radiographic and radiomics features were collected and used for prediction model establishment via Orange Data Mining Toolbox. P < 0.05 was set as statistically significant. RESULTS: For total, 530 ccRCC cases were included. The IL-23 group was significantly associated with survival, histologic grade, AJCC tumor stage, AJCC cancer stage, and plasma calcium level. Except for Treg and other T cells, IL-23 showed correlation with NK cell, mast cell, monocyte infiltration. Axial length was the only significant radiographic measurement between IL-23 groups. The radiomics features established an IL-23 group prediction model with the highest 10-fold cross-verification AUC of 0.842. CONCLUSION: The clear cell renal cell carcinoma IL-23 expression level had prognosis and immune microenvironment correlation and could be predicted by pre-operative radiomics features.

MANIEA: a microbial association network inference method based on improved Eclat association rule mining algorithm.

MOTIVATION: Modeling microbiome systems as complex networks are known as the problem of network inference. Microbial association network inference is of great significance in applications on clinical diagnosis, disease treatment, pathological analysis, etc. However, most current network inference methods focus on mining strong pairwise associations between microorganisms, which is defective in reflecting the comprehensive interactive patterns participated by multiple microorganisms. It is also possible that the microorganisms involved in the generated network are not dominant in the microbiome due to the mere focus on the strength of pairwise associations. Some scholars tried to mine comprehensive microbial associations by association rule mining methods, but the adopted algorithms are relatively basic and have severe limitations such as low calculation efficiency, lacking the ability of mining negative correlations and high redundancy in results, making it difficult to mine high-quality microbial association rules and accurately infer microbial association networks. RESULTS: We proposed a microbial association network inference method 'MANIEA' based on the improved Eclat algorithm for mining positive and negative microbial association rules. We also proposed a new method for transforming association rules into microbial association networks, which can effectively demonstrate the co-occurrence and causal correlations in association rules. An experiment was conducted on three authentic microbial abundance datasets to compare the 'MANIEA' with currently popular network inference methods, which demonstrated that the proposed 'MANIEA' show advantages in aspects of correlation forms, computation efficiency, adjustability and network characteristics. AVAILABILITY AND IMPLEMENTATION: The algorithms and data are available at: https://github.com/MaidiL/MANIEA.

Estimating the transmissibility of hand, foot, and mouth disease by a dynamic model.

OBJECTIVE: Hand, foot, and mouth disease (HFMD) is a serious public health issue in many countries; however, its transmissibility in county-level outbreaks remains unclear. The aim of this study is to estimate the transmissibility of HFMD epidemics on both city level and county level, for a better understanding of the transmission dynamics of HFMD epidemics. STUDY DESIGN: Simulation based on data obtained from the China Information System for Disease Control and Prevention. METHODS: The weekly number of reported HFMD cases from April 2009 to December 2017 in nine regions of Changsha City was collected. A susceptible-infectious-recovered model was used to estimate the transmissibility of HFMD. The reproduction number of reported cases during the ascending (denoted as Rasc) and descending (denoted as Rdes) period was used to describe the transmissibility of HFMD. RESULTS: The Rasc and Rdes for HFMD in Changsha was 1.44 (95% confidence interval [CI]: 1.41-1.48) and 0.71 (95% CI: 0.69-0.73), respectively. There was no statistical significance of Rasc values among nine regions (F = 1.056, P = 0.396), nor of Rdes values among nine regions (F = 1.676, P = 0.106). The average Rasc (1.53, 95% CI: 1.46-1.61) from 2009 to 2012 was higher than the one (1.37, 95% CI: 1.34-1.40) from 2013 to 2017 (t = 3.974, P < 0.001), but the average Rdes (0.67, 95% CI: 0.63-0.70) from 2009 to 2012 was lower than the one (0.74, 95% CI: 0.73-0.76) from 2013 to 2017 (t = -3.751, P < 0.001). CONCLUSIONS: The epidemic of HFMD in Changsha City is still grim, and integrated strategies should be taken for controlling and preventing HFMD.

[My personal idea on acupuncture and moxibustion (acu-moxibustion) literature of the Republic of China not recorded in the General Catalog of the Ancient Chinese Medical Books].

In addition to the collected books in the General Catalog of Ancient Chinese Medical Books, there are lots of acu-moxibustion literature of the Republic of China period scattered among the people which are not carried in this Catalog, some of them are rare and precious ones. In 1933, the first issue of Acu-moxibustion Journal was published and became the first professional Journal of acupuncture and moxibustion in China, 35 issues were published at that time, with many monographs on acu-moxibustion carried in its "special column". Meanwhile, other acupuncturists from different regions also established acu-moxibustion associations or schools and edited all kinds of acupuncture moxibustion teaching materials in order to develop acu-moxibustion education. In a word, the acu-moxibustion literature of the Republic of China were not only rich in forms and contents, but also combined with regional characteristics. Therefore, it should be pay more attention on that field and do further study.

Wheat germ agglutinin modified liposomes for the photodynamic inactivation of bacteria.

Photodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria-targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin-loaded liposomes using an activated phospholipid containing N-hydroxylsuccinimide residue. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA- modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA- modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA- modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram-positive and Gram-negative bacterial cells.

Fast high-throughput screening of temoporfin-loaded liposomal formulations prepared by ethanol injection method.

A new strategy for fast, convenient high-throughput screening of liposomal formulations was developed, utilizing the automation of the so-called ethanol-injection method. This strategy was illustrated by the preparation and screening of the liposomal formulation library of a potent second-generation photosensitizer, temoporfin. Numerous liposomal formulations were efficiently prepared using a pipetting robot, followed by automated size characterization, using a dynamic light scattering plate reader. Incorporation efficiency of temoporfin and zeta potential were also detected in selected cases. To optimize the formulation, different parameters were investigated, including lipid types, lipid concentration in injected ethanol, ratio of ethanol to aqueous solution, ratio of drug to lipid, and the addition of functional phospholipid. Step-by-step small liposomes were prepared with high incorporation efficiency. At last, an optimized formulation was obtained for each lipid in the following condition: 36.4 mg·mL(-1) lipid, 13.1 mg·mL(-1) mPEG(2000)-DSPE, and 1:4 ethanol:buffer ratio. These liposomes were unilamellar spheres, with a diameter of approximately 50 nm, and were very stable for over 20 weeks. The results illustrate this approach to be promising for fast high-throughput screening of liposomal formulations.

Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy.

Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.

Improved absorption of salmon calcitonin by ultraflexible liposomes through intranasal delivery.

The objective of this work was to explore the potential of ultraflexible liposomes as carriers for improving the absorption of salmon calcitonin (sCT) through intranasal administration. The average diameters of positively charged ultraflexible liposomes ranged from about 73 to 99 nm, while those of negatively charged ones were 114 and 157.6 nm, respectively. The content of sodium deoxycholate in liposomes markedly affected the size and encapsulated efficiency of liposomes. The absorption of sCT through intranasal administration was evaluated by hypocalcemic efficacy in rats. The total Ca decrease D% of sCT-loaded ultraflexible liposomes with positive and negative charges were significantly bigger than that of sCT solution, while there was no significant difference in the hypocalcemic efficacy between plain liposome and sCT solution. Unexpectedly, the hypocalcemic efficacy of sCT-loaded ultraflexible liposomes with positive charges was not significantly better than those with negative charges. The decrease rate and extent of the serum calcium level for subcutaneous injection of sCT solution were almost equivalent to those for intranasal administration of negatively and positively charged ultraflexible liposomes within the first 2h, indicating that the ultraflexible liposomes could quickly enhance the penetration of the drug during their residence in the nasal cavity. The results of the toxicity of sCT-loaded ultraflexible liposomes to nasal mucosa demonstrated that the ultraflexible liposomes exerted slight toxicity on the nasal mucosa. On an overall evaluation, the ultraflexible liposomes may be a useful vehicle for intranasal delivery of sCT.

Self-assembled polymeric micellar nanoparticles as nanocarriers for poorly soluble anticancer drug ethaselen.

A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 µg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-ß-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.