Comparative efficacy of sequential treatment and open abdomen approaches for corrosive abdominal hemorrhage due to inadequate drainage of duodenal leakage: a cohort study.

BACKGROUND: Intra-abdominal bleeding resulting from inadequate drainage of duodenal leakage (DL) is typically caused by the corrosiveness of duodenal fluid. Open abdomen (OA) treatment addresses both the drainage and bleeding simultaneously. However, a sequential treatment (ST) approach involving hemostasis through transcatheter arterial embolization (TAE) followed by percutaneous drainage of source control has emerged as an alternative method. This study aimed to evaluate the prognosis of ST in cases of DL-induced intra-abdominal bleeding. METHODS: This retrospective cohort study included 151 participants diagnosed with DL-induced intra-abdominal bleeding from January 2004 to December 2010, and January 2013 to December 2021. The ST and OA groups were established based on the treatment method applied. Propensity score-matching (PSM) matched patients in the ST group with those in the OA group. RESULTS: Among the 151 patients, 61 (40.4%) died within 90 days after the bleeding episode. ST was associated with a lower mortality rate (28.2% vs. 51.3% adjusted odds ratio [OR] = 0.34; 95% confidence interval [CI] 0.17-0.68; P = 0.003) compared to OA. Following PSM, ST remained the only factor associated with reduced mortality (OR = 0.32; 95% CI 0.13-0.75; P = 0.009). Moreover, ST demonstrated a higher rate of initial hemostasis success before (90.1% [64/71] vs. 77.5% [62/80]; adjusted OR = 2.84; 95% CI 1.07-7.60; P = 0.04) and after PSM (94.4% [51/54] vs. 77.8% [42/54], adjusted OR = 3.85; 95% CI 2.15-16.82; P = 0.04). Additionally, ST was associated with a lower incidence of rebleeding within 90 days after the initial bleeding, before (7 vs. 23; adjusted OR 0.41; 95% CI 0.18-0.92; P = 0.03) and after PSM (5 vs. 14; adjusted OR 0.37; 95% CI 0.15-0.93; P = 0.03). CONCLUSIONS: Applying ST involving TAE and subsequent percutaneous drainage might be superior to OA in lowering the mortality in DL-induced intra-abdominal hemorrhage.

ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer.

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5's function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5's demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer.

Effect of placing double-lumen irrigation-suction tube on closure of anastomotic defect following rectal cancer surgery.

PURPOSE: This study aimed to investigate the effect of placement of double-lumen irrigation-suction tubes (DLIST) on the closure of anastomotic defect (AD) after rectal cancer surgery. METHODS: The study was carried out at two centers managed by one surgeon, both adopted the same treatments. Patients with postoperative AD after rectal cancer surgery from January 2011 to June 2020 were eligible and were divided into a passive drainage (PD) group and a DLIST group according to whether the PD, placed in the rectal cancer surgery, had been replaced with the DLIST. The effect of DLIST on the AL was evaluated. RESULT: There distributed 76 patients in the DLIST group and 52 in the PD group. A higher closure rate was reported in the DLIST group (46 patients in DLIST group, for a closure rate of 60.5%, and 21 patients in PD group, for a closure rate of 40.4%. HR = 3.05; 95% CI: 1.79-5.19; P < 0.001). Both length of stay and costs of the treatment in the DLIST group were lower (54 days [interquartile range, IQR: 41-17] days vs. 112 days [IQR: 66-27] days, P = 0.005; and $18,721 [IQR: $14,982-4,960] vs. $40,840 [IQR: $20,932-50,529], P < 0.001). CONCLUSION: Placement of DLIST might serve as an effective method for treating AD following rectal cancer surgery. In comparison with PD, it costs lower to apply DLIST in the treatment of AD and the length of stay is shorter.

Duration of postoperative hyperlactatemia has predictive value in recurrent fistula after major definitive surgery for intestinal fistula.

PURPOSE: The present study aimed to identify the predictive value of duration of postoperative hyperlactatemia in screening patients at high risk of recurrent fistula after major definitive surgery (DS) for intestinal fistula. METHODS: If the initial postoperative lactate (IPL) > 2 mmol/L, DS was defined as major definitive surgery. The 315 enrolled patients with major DS were divided into group A (2 mmol/L < IPL ≤ 4 mmol/L), group B (mmol/L < IPL ≤ 6 mmol/L), and group C (IPL > 6 mmol/L). The characteristics of patients were collected, and the duration of postoperative hyperlactatemia was analyzed. According to the occurrence of recurrent fistula (RF), patients were further divided into RF group A, and Non-RF group A; RF group B, and Non-RF group B; and RF group C, and Non-RF group C. RESULTS: The duration of postoperative hyperlactatemia was comparable between the RF group A and the Non-RF group A [12 (IQR: 12-24) vs 24 (IQR: 12-24), p = 0.387]. However, the duration of hyperlactatemia was associated with RF in group B (adjusted OR = 1.061; 95% CI: 1.029-1.094; p < 0.001) and group C (adjusted OR = 1.059; 95% CI: 1.012-1.129; p = 0.017). In group B, the cutoff point of duration of 42 h had the optimal predictive value (area under ROC = 0.791, sensitivity = 0.717, specificity = 0.794, p < 0.001). In group C, the cutoff point of duration of 54 h had the optimal predictive value (area under ROC = 0.781, sensitivity = 0.730, specificity = 0.804, p < 0.001). CONCLUSION: The duration of postoperative hyperlactatemia has a value in predicting RF in patients with an IPL of more than 4 mmol/L after major definitive surgery for intestinal fistula.

Aspirin Reduces Colorectal Tumor Development in Mice and Gut Microbes Reduce its Bioavailability and Chemopreventive Effects.

BACKGROUND & AIMS: Alterations in the intestinal microbiota affect development of colorectal cancer and drug metabolism. We studied whether the intestinal microbiota affect the ability of aspirin to reduce colon tumor development in mice. METHODS: We performed studies with APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium to induce colorectal carcinogenesis. Some mice were given antibiotics to deplete intestinal microbes, with or without aspirin, throughout the entire experiment. Germ-free mice were studied in validation experiments. Colon tissues were collected and analyzed by histopathology, quantitative reverse-transcription polymerase chain reaction, and immunoblots. Blood samples and gut luminal contents were analyzed by liquid chromatography/mass spectrometry and an arylesterase activity assay. Fecal samples were analyzed by 16S ribosomal RNA gene and shotgun metagenome sequencing. RESULTS: Administration of aspirin to mice reduced colorectal tumor number and load in APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium that had been given antibiotics (depleted gut microbiota), but not in mice with intact microbiota. Germ-free mice given aspirin developed fewer colorectal tumors than conventionalized germ-free mice given aspirin. Plasma levels of aspirin were higher in mice given antibiotics than in mice with intact gut microbiota. Analyses of luminal contents revealed that aerobic gut microbes, including Lysinibacillus sphaericus, degrade aspirin. Germ-free mice fed L sphaericus had lower plasma levels of aspirin than germ-free mice that were not fed this bacterium. There was an inverse correlation between aspirin dose and colorectal tumor development in conventional mice, but this correlation was lost with increased abundance of L sphaericus. Fecal samples from mice fed aspirin were enriched in Bifidobacterium and Lactobacillus genera, which are considered beneficial, and had reductions in Alistipes finegoldii and Bacteroides fragili, which are considered pathogenic. CONCLUSIONS: Aspirin reduces development of colorectal tumors in APCmin/+ mice and mice given azoxymethane and dextran sulfate sodium, depending on the presence of intestinal microbes. L sphaericus in the gut degrades aspirin and reduced its chemopreventive effects in mice. Fecal samples from mice fed aspirin were enriched in beneficial bacteria, with reductions in pathogenic bacteria.

Early Enteral Nutrition Could Reduce Risk of Recurrent Leakage After Definitive Resection of Anastomotic Leakage After Colorectal Cancer Surgery.

BACKGROUND: The present study aimed to evaluate the effect of early enteral nutrition (EEN) after definitive resection of anastomotic leakage (DRAL) resulting from a sigmoid colon or rectal cancer radical resection. METHODS: This was a prospective cohort study performed at our center. From January 2014 to May 2016, every patient received a standard postoperative nutritional protocol (SPNP) after DRAL and was included into SPNP group. From June 2016 to December 2018, all patients received an EEN after DRAL and were included into EEN group. The effect of postoperative EEN was evaluated. RESULTS: There were a final total of 133 patients enrolled in our study. There were 70 patients in the SPNP group, and 63 patients in the EEN group. There were 12 cases (19.05%) with a recurrent leakage in the EEN group, and 28 cases (40%) in the SPNP group. The recurrent rate was associated with EEN (HR = 0.417, 95% CI 0.196-0.890, p = 0.024). The median defecation time in the EEN group was 5(4-7) days, while in the SPNP group was 7(6-8.25) days. The defecation was associated with EEN (HR = 1.588, 95% CI 1.080-2.336, p = 0.019), as well. CONCLUSION: EEN could reduce the recurrent leakage rate and defecation time after definitive resection of anastomotic leakage resulting from sigmoid colon or rectal cancer radical resection.

Effects of different preoperative enteral nutrition feeding routes on the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula.

PURPOSE: The purpose of this study is to investigate the effects of different preoperative enteral nutrition feeding routes on the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula. METHODS: From January 2015 to June 2019, patients with small intestinal fistula and receiving a definitive surgery were enrolled. According to the feeding route, patients were divided into a nasointestinal tube group and a nasogastric tube group. Clinical characteristics of the two groups were analyzed, and the influence of the two route on the recovery of gastrointestinal function was evaluated. RESULT: A total of 151 patients were enrolled in our study. There were 49 patients in the nasogastric tube group, and 102 patients in the nasointestinal tube group. Enteral nutrition via nasogastric feeding route had a positive effect on shortening the duration of gastrointestinal decompression (adjusted HR = 2.488, 95% CI: 1.692-3.659, P < 0.001). After propensity matching (PM), 44 patients were enrolled (22 vs 22). EN via nasogastric tube was a positive factor for getting rid of gastrointestinal decompression (adjusted HR = 3.563, 95% CI: 1.639-7.746, P = 0.001). CONCLUSION: Preoperative enteral nutrition via nasogastric route can reduce the duration of gastrointestinal decompression after definitive surgery for small intestinal fistula.

Transcatheter Arterial Embolization in the Treatment of Abdominal Bleeding in Patients Being Treated with Open Abdomen Due to Duodenal Fistula.

BACKGROUND: This study aimed to investigate the transcatheter arterial embolization (TAE) in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula. METHODS: This was a retrospective study performed at our center. From January 2005 to November 2010, all patients with abdominal bleeding were treated with surgical hemostasis (SH) and included in SH group. From January 2012 to December 2018, all patients with a bleeding were treated with TAE and included in the TAE group. Clinical data were reviewed and compared between the two groups. The effect of TAE in the management of abdominal bleeding was evaluated. RESULTS: A total of 131 patients were enrolled, and there were 64 in the SH group and 67 in the TAE group. The success rate of hemostasis was higher in the TAE group (89.55% vs. 73.44%, adjusted OR = 4.065, 95% CI 1.336-12.336, P = 0.013). Moreover, the recognition rate of hemorrhagic vessels in the TAE group was higher (91.04 vs. 51.56; P < 0.001). The re-bleeding occurred in 20 patients, 7(11.67%) in the TAE group and 13(27.66%) in the SH group. The re-bleeding rate in SH group was higher (adjusted HR = 2.564, 95% CI 1.023-6.428, P = 0.045) CONCLUSIONS: TAE is an effective method in treatment of abdominal bleeding in patients being treated with open abdomen due to duodenal fistula.

A double-lumen irrigation-suction tube placed during operation could reduce the risk of grade C anastomotic leakage resulting from selective sigmoid colon cancer radical resection.

AIM: This study investigated the effect of a double-lumen irrigation-suction tube in reducing the incidence of grade C anastomotic leakage (AL) resulting from a selective sigmoid colon cancer radical resection. METHOD: This multicenter retrospective cohort study reviewed data of patients receiving sigmoid colon cancer radical resection from January 2010 to November 2019. The enrolled patients were divided into the passive drainage tube group and the double-lumen irrigation-suction tube group, based on the use of a double-lumen irrigation-suction tube or a passive drainage tube during the surgery. The effect of double-lumen irrigation-suction tube on the incidence of grade C anastomotic leakage was evaluated. RESULTS: Of the 761 patients included in the study, 56 patients (7.36%) experienced AL. Of the 56 patients, 22 were diagnosed with grade C AL. The double-lumen irrigation-suction tube was a protective factor for forming a grade C AL compared with the passive drainage tube (OR = 0.194, 95% CI: 0.055-0.686, p = 0.011). Of the 34 patients with grade A or B AL, 26 patients had spontaneous closure-19 in the double-lumen irrigation-suction tube group and 7 in the passive drainage tube group. The double-lumen irrigation-suction tube (multivariable HR = 3.418, 95% CI: 1.43-11.203, p = 0.038) was associated with spontaneous closure of grade A or B AL. CONCLUSION: Placing a double-lumen irrigation-suction tube may reduce the risk of grade C AL resulting from a selective sigmoid colon cancer radical resection. However, this study had substantial selection bias and the results should be reconfirmed by a randomized clinical trial.

Gut mucosal virome alterations in ulcerative colitis.

OBJECTIVE: The pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC. DESIGN: Deep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2. RESULTS: In UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC. CONCLUSION: We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.

Restaging of locally advanced rectal cancer with magnetic resonance imaging and endoluminal ultrasound after preoperative chemoradiotherapy: a systemic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging and endoluminal ultrasound play an important role in the restaging of locally advanced rectal cancer after preoperative chemoradiotherapy, yet their diagnostic accuracy is still controversial. OBJECTIVE: Meta-analysis was performed to estimate the diagnostic performance of MRI and endoluminal ultrasound. DATA SOURCES: Electronic databases from 1996 to March 2012 were searched. STUDY SELECTION AND INTERVENTIONS: Either MRI or endoluminal ultrasound was used to restage rectal cancer after chemoradiotherapy or radiation. MAIN OUTCOME MEASURES: T category, lymph node, and circumferential resection involvement were measured. RESULTS: The sensitivity estimate for rectal cancer diagnosis (T0) by endoluminal ultrasound (37.0%; 95% CI, 24.0%-52.1%) was higher (p = 0.04) than the sensitivity estimate for MRI (15.3%; 95% CI, 6.5%-32.0%). For T3-4 category, sensitivity estimates of MRI and endoluminal ultrasound were comparable, 82.1% and 87.6%, whereas specificity estimates were poor (53.5% and 66.4%). For lymph node involvement, there was no significant difference between the sensitivity estimates for MRI (61.8%) and endoluminal ultrasound (49.8%). Specificity estimates for MRI and endoluminal ultrasound were 72.0% and 78.7%. For circumferential resection margin involvement, MRI sensitivity and specificity were 85.4% and 80.0%. LIMITATIONS: To identify the heterogeneity, metaregression was performed on covariates. However, few of the covariates were identified to be statistically significant because of the lack of adequate original data. CONCLUSION: Accurate restaging of locally advanced rectal cancer by MRI and endoluminal ultrasound is still a challenge. Identifying T0 rectal cancer by imaging is not reliable. Before performing surgery, restaging is important, but some of the T0-2 patients are likely overestimated as T3-4. Both modalities for lymph node involvement are not very good. Magnetic resonance imaging may be a good method to reassess circumferential resection margin.

Fluid volume overload negatively influences delayed primary facial closure in open abdomen management.

BACKGROUND AND AIM: The open abdomen (OA) is associated with significant morbidity and mortality, and its management poses a formidable challenge. Inability to achieve primary closure of the abdominal wall is one of the most severe complications of this technique. Factors influencing primary fascial closure, however, are unknown. This study aims to explore the influence of fluid volume overload on the application of vacuum-assisted and mesh-mediated fascial traction (VAWCM) in OA treatment. METHODS: A review of patients undergoing OA management using VAWCM technique from January 2006 to November 2011 was performed. Patients with aged <18 y OA treatment for fewer than 5 d and abdominal wall hernia before OA treatment were excluded. RESULTS: Average age was 45 ± 10.1 y and average OA treatment time was 31 ± 6.8 d. The complete fascial closure rate was 60%. The overall mean bodyweight-based fluid overload was 7.2 kg (range: -8.0 to +21.6 kg), representing a mean percent weight gain of 11.5% (range: -9.5% to +27%). Patients with fluid-related weight gain ≥10% had a lower primary facial closure rate than those with <10% (39% versus 77%). And primary facial closure rate seems to further decrease with fluid-related weight gain ≥20%, suggesting a dose-response effect of progressive fluid accumulation. CONCLUSIONS: The VAWCM method provided a high primary fascial closure rate after long-term treatment of OA. Fluid volume overload negatively influences delayed primary facial closure. Judicious intravenous fluid resuscitation should be advocated in the therapy of critically ill patients.

Comparison of short- and long-term outcomes after extralevator abdominoperineal excision and standard abdominoperineal excision for rectal cancer: a systematic review and meta-analysis.

PURPOSE: Whether the introduction of extralevator abdominoperineal excision (ELAPE) improves survival and safety remains controversial. We conducted a systematic review and meta-analysis of all comparative studies to define the efficacy and safety of ELAPE and standard abdominoperineal excision (APE). MATERIALS AND METHODS: A search for all major databases and relevant journals from inception to July 2013 without restriction on languages or regions was performed. Outcome measures were the oncological parameters of circumferential resection margin (CRM) involvement, intraoperative bowel perforation (IOP), and local recurrence, as well as other parameters of blood loss, operative time, length of hospitalization, and postoperative complication. The test of heterogeneity was performed with the Q statistic. RESULTS: A total of 949 patients were included in the meta-analysis. Oncological pooled estimates of intraoperative bowel perforation rate (RR 0.34; 95 % CI 0.21-0.54; P < 0.00001), CRM involvement (RR 0.44; 95 % CI 0.34-0.56; P < 0.00001), and local recurrence (RR 0.32; 95 % CI 0.14-0.74; P = 0.008) all showed outcomes that were significantly lower in ELAPE than in APE. A similar incidence of postoperative complication was attributed to both groups, including overall complication (RR 0.93; 95 % CI 0.66-1.32; P = 0.69), perineal wound complication (RR 0.72; 95 % CI 0.33-1.55; P = 0.39), and urinary dysfunction (RR 1.53; 95 % CI 0.88-2.67; P = 0.13). CONCLUSION: ELAPE has a lower intraoperative bowel perforation rate, positive CRM rate, and local recurrence rate than APE. There is evidence that in selected low rectal cancer patients, ELAPE is a more efficient and equally safe option to replace APE. Due to the inherent limitations of the present study, future randomized controlled trials will be useful to confirm this conclusion.

PEG-modified nano liposomes co-deliver Apigenin and RAGE-siRNA to protect myocardial ischemia injury.

Ischemic heart disease (IHD) is a cardiac disorder in which myocardial damage occurs as a result of myocardial ischemia and hypoxia. Evidence suggests that oxidative stress and inflammatory responses are critical in the development of myocardial ischemia. Therefore, the combination of antioxidant and anti-inflammatory applications is an effective strategy to combat ischemic heart disease. In this paper, polyethylene glycol (PEG)-modified cationic liposomes were used as carriers to deliver apigenin (Apn) with small interfering RNA (siRNA) targeting the receptor for glycosylation end products (RAGE) (siRAGE) into cardiomyocytes to prevent myocardial ischemic injury through antioxidant and anti-inflammatory effects. Our results showed that we successfully prepared cationic PEG liposomes loaded with Apn and siRAGE (P-CLP-A/R) with normal appearance and morphology, particle size and Zeta potential, and good encapsulation rate, drug loading and in vitro release degree. In vitro, P-CLP-A/R was able to prevent oxidative stress injury in H9C2 cells, downregulate the expression of RAGE, reduce the secretion of cellular inflammatory factors and inhibit apoptosis through the RAGE/NF-κB pathway; In vivo, P-CLP-A/R was able to prevent arrhythmia and myocardial pathological injury, and reduce apoptosis and the area of necrotic myocardium in rats. In conclusion, P-CLP-A/R has a protective effect on myocardial ischemic injury and is expected to be a potential drug for the prevention of ischemic heart disease in the future.

Nomogram for predicting intolerable postoperative early enteral nutrition following definitive surgery for small intestinal fistula: a cohort study.

BACKGROUND: This study was designed to develop and validate a nomogram for predicting intolerable early enteral nutrition (EEN) following definitive surgery (DS) for small intestinal fistula. METHODS: A total of 377 patients, recruited from January 2016 to September 2023, was randomly allocated into development ( n =251) and validation ( n =126) groups in a 2:1 ratio. Risk factors were identified using the nomogram. Its performance was assessed based on calibration, discrimination, and clinical utility, with validation confirming its effectiveness. RESULTS: Of the 377 patients, 87 (23.1%) were intolerant to EEN, including 59 (23.1%) in the development cohort and 28 (22.1%) in the validation cohort ( P =0.84). Four factors were identified as predictive of intolerable EEN: severe abdominal adhesion, deciliter of blood loss during DS, human serum albumin (Alb) input >40 g during and within 48 h post-DS, and the visceral fat area (VFA)/total abdominal muscle area index (TAMAI) ratio. The model demonstrated excellent discrimination, with a C-index of 0.79 (95% CI: 0.74-0.87, including internal validation) and robust calibration. In the validation cohort, the nomogram showed strong discrimination (C-index=0.77; 95% CI: 0.64-0.87) and solid calibration. Decision curve analysis affirmed the nomogram's clinical utility. CONCLUSION: This research introduces a nomogram that enables the individualized prediction of intolerable EEN following DS for small intestinal fistula, demonstrating a possible clinical utility.

Biological effects and mechanism of ß-amyloid aggregation inhibition by penetrable recombinant human HspB5-ACD structural domain protein.

Alzheimer's disease (AD) is a global medical challenge. Studies have shown that neurotoxicity caused by pathological aggregation of ß-amyloid (Aß) is an important factor leading to AD. Therefore, inhibiting the pathological aggregation of Aß is the key to treating AD. The recombinant human HspB5-ACD structural domain protein (AHspB5) prepared by our group in the previous period has been shown to have anti-amyloid aggregation effects, but its inability to penetrate biological membranes has limited its development. In this study, we prepared a recombinant fusion protein (T-AHspB5) of TAT and AHspB5. In vitro experiments showed that T-AHspB5 inhibited the formation of Aß1-42 protofibrils and had the ability to penetrate the blood-brain barrier; in cellular experiments, T-AHspB5 prevented Aß1-42-induced oxidative stress damage, apoptosis, and inflammatory responses in neuronal cells, and its mechanism of action was related to microglia activation and mitochondria-dependent apoptotic pathway. In animal experiments, T-AHspB5 improved memory and cognitive dysfunction and inhibited pathological changes of AD in APP/PS1 mice. In conclusion, this paper is expected to reveal the intervention mechanism and biological effect of T-AHspB5 on pathological aggregation of Aß1-42, provide a new pathway for the treatment of AD, and lay the foundation for the future development and application of T-AHspB5.

Recombinant human HspB5-ACD structural domain inhibits neurotoxicity by regulating pathological α-Syn aggregation.

The treatment of Parkinson's disease is a global medical challenge. α-Synuclein (α-Syn) is the causative protein in Parkinson's disease and is closely linked to its progression. Therefore, inhibiting the pathological aggregation of α-Syn and its neurotoxicity is essential for the treatment of Parkinson's disease. In this study, α-Syn and recombinant human HspB5-ACD structural domain protein (AHspB5) were produced using the BL21(DE3) E. coli prokaryotic expression system, and then the role and mechanism of AHspB5 in inhibiting the pathological aggregation of α-Syn and its neurotoxicity were investigated. As a result, we expressed α-Syn and AHspB5 proteins and characterised the proteins. In vitro experiments showed that AHspB5 could inhibit the formation of α-Syn oligomers and fibrils; in cellular experiments, AHspB5 could prevent α-Syn-induced neuronal cell dysfunction, oxidative stress damage and apoptosis, and its mechanism of action was related to the TH-DA pathway and mitochondria-dependent apoptotic pathway; in animal experiments, AHspB5 could inhibit behavioural abnormalities, oxidative stress damage and loss of dopaminergic neurons. In conclusion, this work is expected to elucidate the mechanism and biological effects of AHspB5 on the pathological aggregation of α-Syn, providing a new pathway for the treatment of Parkinson's disease and laying the foundation for recombinant AHspB5.

Lycorine inhibits Ang II-induced heart remodeling and inflammation by suppressing the PI3K-AKT/NF-κB pathway.

BACKGROUND: Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. METHODS: Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. RESULTS: LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. CONCLUSION: Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.

Visceral to subcutaneous fat area ratio predicts severe abdominal adhesions in definitive surgery for anastomotic fistula after small intestine resection.

Abdominal adhesions manifests following abdominal infections triggered by intestinal fistulas. The severity of such adhesions depends on the extent of fiber deposition and peritoneal fibrinolysis following peritoneal injury, which may be influenced by sustained inflammation within the abdominal cavity. In this regard, the visceral-to-subcutaneous fat area (VFA/SFA) ratio has been implicated as a potential marker of inflammation. This study aimed to explore the relationship between VFA/SFA and abdominal adhesions. This multicenter study was conducted across four tertiary institutions and involved patients who had undergone definitive surgery (DS) for intestinal fistula from January 2009 and October 2023. The presence of abdominal adhesions was determined intraoperatively. VFA/SFA was investigated as a potential risk factor for severe adhesions. The study comprised 414 patients with a median age of 50 [interquartile range (IQR) 35-66] years and a median body mass index of 20.0 (IQR 19.2-22.4) kg/m2, including 231 males with a median VFA/SFA of 1.0 (IQR 0.7-1.2) and 183 females a median VFA/SFA of 0.8 (0.6-1.1). VFA/SFA was associated with severe abdominal adhesions in males [odds ratio (OR) = 3.34, 95% CI 1.14-9.80, p = 0.03] and females (OR = 2.99, 95% CI 1.05-8.53, p = 0.04). J-shaped association between VFA/SFA ratio and severe adhesions was revealed in both sex. The increasing trend can be revealed when OR more than 0.8, and 0.6 in males and females respectively. Preoperative VFA/SFA demonstrates predictive value for statues of severe abdominal adhesions in DS for anastomotic fistula after small intestine resection.