Long-term outcomes of intestinal penetrating Crohn's disease following successful nonoperative management.

There is a paucity of data on the surgical or medical treatment for abscess/fistula complicating Crohn's disease after successful nonsurgical management. We conducted a cohort study to investigate the long-term outcomes and the risk factors for the requirement of subsequent surgical intervention in Crohn's disease patients with complicating fistulas/abscess following successful nonsurgical management. Data were collected on penetrating Crohn's disease experiencing successful nonsurgical treatment between December 2012 and December 2021. Long-term outcomes and risk factors of surgery were assessed by univariate and multivariate analysis, and subgroup analysis was performed based on penetrating phenotype including abscess, fistula, and phlegmon. A total of 523 penetrating Crohn's disease patients; there were 390, 125, and 60 patients complicated with fistulas, abscess, and phlegmon, respectively. Long-term outcomes showed that BMI < 18.5 (kg/m2), the recurrent abscess, and stricture were independent risk factors of surgery. Biologics and resolution of abscess were independent protective factors of surgery. Furthermore, in 399 patients undergoing early surgery, stricture and BMI < 18.5 (kg/m2) were independent risk factors, and biologics and abscess resolution were protective of the early surgery. Subgroup analysis based on fistula, abscess, and phlegmon phenotype also demonstrated that concomitant stricture was an independent risk factor and the use of biologics was protective of surgical resection. Our data indicate that biologics can delay the requirement of surgery and may be given to patients with penetrating complicating Crohn's disease who have been successfully treated nonoperatively, but surgical resection should be considered in the setting of malnutrition and stenosis formation.

Synergistic Inhibitions of Gram-negative Bacteria by Combination Treatment with Ciprofloxacin and a Novel Glucolipid.

Psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-4032 derived from Antarctica was cultivated under 16 ℃ to produce a new glucolipid compound (1). Its structure was elucidated by analysis of detailed spectroscopic data, acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization, and 13C NMR quantum chemical calculations. Though compound 1 did not show inhibitory activity against bacteria, it can reduce the minimum inhibitory concentration (MIC) of ciprofloxacin against Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli, and Salmonella paratyphi by 1024, 256 and 256-fold. Compound 1 showed potential as a synergistically inhibiting adjuvant in co-administration with antibiotic to enhance antibacterial activities.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model.

JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Carbazole and Quinazolinone Derivatives from a Fluoride-Tolerant Streptomyces Strain OUCMDZ-5511.

Six new 9H-carbazole derivatives (1-6) and nine previously reported compounds (7-15) were isolated from a fermented solid medium of the Thailand mangrove-derived Streptomyces strain, OUCMDZ-5511, under fluoride stress. Compounds 2-5, 12, and 15 were exclusively present in the fluoride-supplemented fermentation medium, while compounds 7-9, 13, and 14 were newly discovered natural products. The molecular structures of the compounds were identified by a spectroscopic analysis. The new compound 2 displayed antiquorum sensing activity against Chromobacterium violaceum ATCC 12472 by reducing the violacein production and inhibiting the biofilm formation in a concentration-dependent manner. The study revealed that compound 2 could be a novel potential inhibitor of quorum sensing.

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review.

Neurodegenerative diseases refer to a battery of medical conditions that affect the survival and function of neurons in the brain, which are mainly presented with progressive loss of cognitive and/or motor function. Acupuncture showed benign effects in improving neurological deficits, especially on movement and cognitive function impairment. Here, we reviewed the therapeutic mechanisms of acupuncture at the neural circuit level in movement and cognition disorders, summarizing the influence of acupuncture in the dopaminergic system, glutamatergic system, γ-amino butyric acid-ergic (GABAergic) system, serotonergic system, cholinergic system, and glial cells at the circuit and synaptic levels. These findings can provide targets for clinical treatment and perspectives for further studies.

Acupuncture for insomnia symptoms in hypertensive patients: a systematic review and meta-analysis.

Purpose: In the realm of pain management, traditional Chinese medicine, specifically acupuncture, has garnered increasing attention. This meta-analysis pioneers the evaluation of acupuncture's effectiveness in treating insomnia among hypertensive patients. Methods: We conducted a comprehensive search across several databases-PubMed, Web of Science, Cochrane Library, WANFANG, China National Knowledge Infrastructure (CNKI), Sinomed, and the Chinese Journal of Science and Technology (VIP). Additionally, forward and backward articles of studies published from the inception of these databases until 10 September 2023, were reviewed. This systematic review and meta-analysis included all randomized controlled trials (RCTs) focusing on acupuncture for insomnia in hypertensive patients, without imposing language or date restrictions. We rigorously assessed all outcome measures reported in these trials. The evidence was synthesized by calculating the difference between mean differences (MD) in symptom change. The quality of the evidence was determined using the Cochrane Risk of Bias tool. This study is registered with PROSPERO under number CRD42023461760. Results: Our analysis included 16 RCTs, comprising 1,309 patients. The findings revealed that acupuncture was significantly more effective than the control group in reducing insomnia symptoms, as indicated by a greater decrease in the PSQI score (MD = -3.1, 95% CI [-3.77 to -2.62], p < 0.00001). Additionally, improvements in both systolic and diastolic blood pressure were more pronounced in the acupuncture group compared to the control group (SBP: MD = -10.31, 95% CI [-16.98 to -3.64], p = 0.002; DBP: MD = -5.71, 95% CI [-8.19 to -3.23], p < 0.00001). These results suggest that acupuncture not only improves sleep quality but also lowers blood pressure in patients suffering from hypertension and insomnia. Further research is warranted to elucidate optimal acupuncture points and the duration of treatment for maximized therapeutic effect.Systematic review registration:https://www.crd.york.ac.uk/prospero, CRD42023461760.

Five previously undescribed citrinin derivatives from the endophytic fungus Penicillium citrinum GZWMJZ-836.

Penicillium citrinum GZWMJZ-836 is an endophytic fungus from Drynaria roosii Nakaike. Five previously undescribed citrinin derivatives (1-5) and six intermediates related to their biosynthesis (6-11) were obtained from the extract of this strain's solid fermentation using multiple column chromatography separations, including high-performance liquid chromatography. The structures of these compounds were determined through comprehensive spectroscopic analyses, primarily using NMR and HRESIMS data. The stereochemistry was mainly confirmed by ECD calculations, and the configurations of C-7' in compounds 4 and 5 were determined using 13C NMR calculations. Compounds 4-5 and 8 showed antibacterial activity against five strains, with minimum inhibitory concentration values ranging from 7.8 to 125 µM. Compounds 4 and 7 exhibited inhibitions against three plant pathogenic fungi, with IC50 values ranging from 66.6 to 152.1 µM. Additionally, a putative biosynthetic pathway for compounds 1-5 derived from citrinin was proposed.

Prophylactic Intra-abdominal Drainage is Associated With Lower Postoperative Complications in Patients With Crohn's Disease: A Randomized Controlled Trial.

BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma.

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

Structurally Diverse Macrolactams from an Antarctic Streptomyces Species.

Twelve new polyenic macrolactams, cyclamenols G-R (1 and 3-13), together with the known analogue cyclamenol A (2), were isolated from Streptomyces sp. OUCMDZ-4348. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations, chemical derivatizations, and Mosher's methods. The sequenced genome of OUCMDZ-4348 revealed the putative biosynthetic gene cluster of cyclamenols. It was proposed that the polycyclic natural products, cyclamenols H-R, might be formed from cyclamenols A and G through nonenzymatic intramolecular cycloadditions and oxidative cyclizations.

TBHP Mediated C-N Bond Cleavage of Tertiary Amines toward the Synthesis of Oxalamides and α,ß-Epoxy Amides.

An efficient and convenient method for the synthesis of oxalamides by the reaction of ß-ketoamides with tertiary amines and TBHP was developed. A variety of ß-ketoamides and tertiary amines substrates were well-tolerated in this transformation. Based on the control experiments, a plausible mechanism for this reaction was proposed that involved the tandem oxidation/amination process. In addition, α,ß-epoxy amides could be obtained by adjusting the reaction conditions.

The impact of delayed closure of ileostomy on postoperative complications in patients with Crohn's disease: a case-matched study.

Ileostomy creation is a common procedure to mitigate postoperative complications in Crohn's disease (CD) patients. However, the optimal timing for ileostomy closure remains controversial. This study aims to investigate whether delayed ileostomy closure (> 6 months post formation) affects postoperative complications compared to early closure (≤ 6 months post formation). Consecutive CD patients who underwent ileostomy reversal at a tertiary care center between January 1, 2013, and December 1, 2021, were included. The study compared patients who underwent early ileostomy closure to matched patients undergoing delayed ileostomy closure. The 90-day postoperative complications were compared between the two groups. The study included 352 eligible patients for ileostomy reversion. Our data showed that patients undergoing delayed ileostomy closure had higher incidence of ileostomy-related infectious complications (12% vs. 4%, p = 0.008), a longer postoperative hospital stay (10 days with an IQR of 7-12 days versus 8 days with an IQR of 7-11 days, p = 0.024), and increased rate of ileus (28% versus 15%, p = 0.003). There were 256 patients included after 1:1 propensity score matching. The results revealed no significant differences in postoperative hospital stay, infectious or non-infectious complications except for a statistically significant increase in the incidence of ileus in the delayed closure group (p = 0.01). Patients undergoing delayed ileostomy closure has similar outcomes to early closure in terms of postoperative complications, except for a higher incidence of ileus.

Azathioprine plus exclusive enteral nutrition versus azathioprine monotherapy for the prevention of postoperative recurrence in patients with Crohn's disease: an open-label, single-centre, randomised controlled trial.

BACKGROUND: Azathioprine (AZA) effectively prevents postoperative endoscopic recurrence (ER) in Crohn's disease (CD). However, the efficacy of AZA emerge needs 3 months. Exclusive enteral nutrition (EEN) can maintain remission for CD. The trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. METHODS: Totally, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus a 3-month EEN (AZA+EEN) postoperatively. The primary endpoint was the rate of ER at month 12. Secondary endpoint included the rate of ER at month 3, clinical recurrence (CR), CD activity index (CDAI) scores, fecal calprotectin (FC) and CRP. Quality of life were assessed using Short Form-36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: The patients in the AZA+EEN group exhibited significantly lower rates of ER compared to the AZA group at both months 12 (33.3% [13/39] vs 63.2% [24/38], P=0.009) and months 3 (8.6% [3/35] vs 28.1% [9/32], P=0.037) post-surgery. The rates of CR between the two groups at month-3 and month-12 were similar. The CDAI scores, FC, albumin level and CRP were all comparable between the 2 groups. The quality of life was significantly higher in the AZA group than that of the AZA+EEN group at month 3 but became comparable from month 5 to 12 postoperatively. CONCLUSION: In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted.

A nomogram to predict stoma creation in elective surgical resection for penetrating Crohn's disease.

BACKGROUNDS: The decision to perform a stoma during surgical resection of penetrating Crohn's disease (CD) is a critical consideration. The objective of this study was to identify factors that influence stoma creation and develop a predictive nomogram model to assist surgeons in making optimal surgical decisions. METHODS: A retrospective study was conducted at a tertiary center from December 1, 2012, to December 1, 2021, involving consecutive patients with penetrating CD who underwent elective surgical resection. The LASSO regression method was used to select preoperative predictors, and a nomogram was constructed using multivariate logistic regression. The performance of the nomogram was validated in an internal cohort by assessing its discrimination, calibration, and clinical usefulness. RESULTS: The study included 405 cases in the training group and 135 cases in the validation group. Nine risk factors for stoma formation were identified, including disease location, fistula resulted from previous anastomosis, absence of preoperative exclusive enteral nutrition support, albumin levels below 35 g/L, C-reactive protein levels above 10 mg/L, hemoglobin levels below 100 g/L, perianal disease, internal fistula, and surgical approach. These risk factors were selected using the LASSO regression method, and a nomogram was developed based on them. The area under the curve and the coefficient of determination (R2 ) of the nomogram were 0.821 and 0.394, respectively. And the nomogram demonstrated good performance in the validation cohort. CONCLUSIONS: The nomogram exhibited good predictive ability for stoma formation during elective surgical resection for penetrating CD, which can assist surgeons in making informed clinical decisions.

Nanoparticle Deep-Subwavelength Dynamics Empowered by Optical Meron-Antimeron Topology.

Optical meron is a type of nonplanar topological texture mainly observed in surface plasmon polaritons and highly symmetric points of photonic crystals in the reciprocal space. Here, we report Poynting-vector merons formed at the real space of a photonic crystal for a Γ-point illumination. Optical merons can be utilized for subwavelength-resolution manipulation of nanoparticles, resembling a topological Hall effect on electrons via magnetic merons. In particular, staggered merons and antimerons impose strong radiation pressure on large gold nanoparticles (AuNPs), while focused hot spots in antimerons generate dominant optical gradient forces on small AuNPs. Synergistically, differently sized AuNPs in a still environment can be trapped or orbit in opposite directions, mimicking a coupled galaxy system. They can also be separated with a 10 nm precision when applying a flow velocity of >1 mm/s. Our study unravels a novel way to exploit topological textures for optical manipulation with deep-subwavelength precision and switchable topology in a lossless environment.

Inequities Along the Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis Services Continuum for Black Women in the United States, 2015-2020.

OBJECTIVE: To estimate the number of women who received human immunodeficiency virus (HIV) and sexually transmitted infection (STI) testing and HIV pre-exposure prophylaxis (PrEP) services by race and ethnicity in seven THRIVE (Targeted Highly Effective Interventions to Reverse the HIV Epidemic)-funded jurisdictions and to estimate associations of age and syphilis and gonorrhea diagnoses with receipt of HIV PrEP services. METHODS: We analyzed data collected from 2015 to 2020 in Birmingham, Alabama; Baltimore City, Maryland; Washington, DC, New Orleans, Louisiana; Brooklyn, New York; Philadelphia, Pennsylvania; and Hampton Roads, Virginia. We compared Black women and women of additional racial and ethnic groups by age, HIV status at enrollment, receipt of STI testing and test positivity, and steps in the PrEP continuum (screened, eligible, referred, linked, and prescribed). We also examined the association of age, syphilis, or gonorrhea with the following steps in the PrEP continuum: screened, referred, linked, and prescribed. RESULTS: Black women made up 69.2% (8,758/12,647) of women served in THRIVE. Compared with non-Black women, Black women were more likely to have a positive test result for syphilis (3.3% vs 2.1%), gonorrhea (4.9% vs 3.5%), chlamydia (5.1% vs 1.9%), or more than one STI (1.4% vs 0.3%). Among women with negative HIV test results or unknown HIV status, Black women were more likely to be screened for PrEP eligibility (88.4% vs 64.9%). Among Black women, the proportion screened for PrEP was higher among those diagnosed with syphilis (97.3%) or gonorrhea (100%) than among those without an STI (88.1% and 87.8%, respectively). Among 219 Black women who presented with syphilis, only 10 (4.6%) were prescribed PrEP; among 407 with gonorrhea, only 11 (2.7%) were prescribed PrEP. CONCLUSION: Although most Black women seeking services received STI testing, the proportion of Black women who were eligible for PrEP and prescribed PrEP was low. To achieve national HIV-prevention goals, it is imperative that Black women have access to PrEP information and services.

Comparison of endoscopic balloon dilation and surgery for duodenal stricture in patients with Crohn's disease.

BACKGROUND: Few studies have compared endoscopic balloon dilation (EBD) and surgery in the treatment of duodenal stricture in patients with Crohn's disease (CD). METHODS: We performed a retrospective study to compare the efficacy and safety among patients with CD-associated duodenal stricture treated with EBD or surgery from October 2013 to December 2021. Univariate and multivariate analyses were performed to evaluate factors associated with recurrence-free or surgery-free survival. RESULTS: A total of 48 eligible patients were included, including 30 patients treated with EBD only and 18 patients treated with surgery. Patients treated with surgery experienced more symptomatic improvement (100% vs. 63.33%, p = 0.003) and significantly longer recurrence-free survival (6.31 [IQR: 3.00-8.39] years vs. 2.96 [IQR: 1.06-5.42] years, p = 0.01) but suffered more postprocedural adverse events (16.67% vs. 0.74% per procedure, p = 0.001). In patients initially treated with EBD (n = 41), a total of 11 (26.83%) required subsequent surgical intervention. Younger age at CD diagnosis (HR = 0.90, 95% CI: 0.81-1.00, p = 0.04) was associated with a higher risk for subsequent surgery. CONCLUSIONS: Surgery for CD-associated duodenal strictures was associated with a longer recurrence-free survival. EBD was safe and effective with minimal postprocedural adverse events but led to a high frequency of recurrence.

HIV Testing and Preexposure Prophylaxis Prescriptions Among U.S. Commercially Insured Transgender Men and Women, 2014 to 2021.

BACKGROUND: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. OBJECTIVE: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. DESIGN: Retrospective analysis of secondary data. SETTING: Merative MarketScan commercial databases from 2014 to 2021. PARTICIPANTS: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. MEASUREMENTS: HIV testing and PrEP use. RESULTS: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. LIMITATION: The findings represent only persons with commercial health insurance who sought health care services for GAHT. CONCLUSION: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. PRIMARY FUNDING SOURCE: None.

Biologic use is not associated with postoperative complications in patients with Crohn's disease undergoing stoma reversion.

PURPOSE: Stoma creation is a common procedure in patients with Crohn's disease (CD), and early prophylaxis with biologics is recommended for high-risk patients. However, the effect of biologic exposure on morbidity after stoma closure remains unknown. Therefore, this study aimed to investigate the impact of biologic use on the occurrence of complications in CD patients following stoma closure. METHODS: Consecutive patients diagnosed with CD who underwent ileostomy reversal at a tertiary care centre between 1 January 2013 and 1 December 2021, were included in the study. The primary outcome was the occurrence of 90-day postoperative complications. RESULTS: The study included 347 eligible patients who underwent ileostomy reversal. There was no significant difference in terms of infectious complications, overall complications or length of postoperative stay between the biologic and non-biologic groups. Multivariate logistic regression analysis identified several predictors of postoperative morbidity, including preoperative haemoglobin levels below 100 g/L, CRP levels above 10 mg/L, anastomotic site, ileostomy-related infectious complications and albumin levels below 35 g/L. CONCLUSIONS: This study demonstrated that the use of biologics is not associated with adverse outcomes. However, such as high CRP levels, ileostomy-related infectious complications, hypoproteinemia, and hemoglobinemia, should be optimized prior to surgery to reduce postoperative morbidities.

Indole Diterpene Derivatives from the Aspergillus flavus GZWMJZ-288, an Endophytic Fungus from Garcinia multiflora.

A new indole diterpene, 26-dihydroxyaflavininyl acetate (1), along with five known analogs (2-6) were isolated from the liquid fermentation of Aspergillus flavus GZWMJZ-288, an endophyte from Garcinia multiflora. The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds 1, 4, and 6 have a good binding affinity with NPC1L1, among which compound 6 exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound 5 showed inhibitory activity against α-glucosidase with an IC50 value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and α-glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.