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Background The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. Methods We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. Results The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. Conclusions An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.

OBJECTIVE Ulcerative colitis (UC) is an independent risk factor for thromboembolism, especially during the perioperative period. This study aimed to determine the effects of perioperative parenteral nutrition (PN) supplemented with fish oil (FO) on coagulation function and postoperative outcomes in patients with UC. METHODS This retrospective cohort included 92 consecutive patients who underwent colectomy for UC. Postoperative coagulation indices and outcomes, including thromboelastography (TEG) findings and comprehensive complication index (CCI), were compared. The relative change in serum D-dimer (ΔD-dimer) levels and maximal amplitude (ΔMA) on TEG were also determined. RESULTS Patients receiving PN supplemented with FO (n = 48) had lower D-dimer (P = .036) levels on postoperative day (POD) 5 and a higher MA (P < 0.001) on POD 1 than those who did not receive it (n = 44). A lower ΔD-dimer level (P = .048) and ΔMA (P < 0.001) were also observed in patients receiving FO. The incidence of major postoperative complications (6.3 vs 22.7%; P = .017) and CCI (20.9 vs 23.4%; P = .044) were significantly lower in patients receiving FO. In multivariate analysis, FO (odds ratio, 0.231; 95% confidence interval, 0.055-0.971; P = .046) was a positive protector of major postoperative complications. CONCLUSION Perioperative PN supplemented with FO improved coagulation function and reduced major postoperative complications in patients with UC requiring colectomy. These results may provide cues in formulating management strategies for preventing thromboembolisms and postoperative complications in patients with UC.

Background: Slits and Robos were associated with the generation of axons of corticospinal tract during the corticospinal tract (CST) remodeling after the cerebral ischemic stroke (CIS). However, little is known about the mechanism of CST remodeling. In this study, we detected the expression of Slits and Robos in middle cerebral artery occlusion (MCAO) rats to investigate the roles of Slits and Robos in the CIS. Methods: MCAO model was established using modified Zea Longa method. Beam walking test (BWT) was conducted to evaluate the motor function. The images of the track of cortical spinal cord beam on day 7, 14 and 21 were observed by anterograde CST tracing. Biopinylated dextan amine (BDA) was used to mark CST anterogradely. Expression of GAP-43 mRNA and GAP-43 protein in cervical spinal cord was detected by Real-Time PCR and Western blot analysis, respectively. The expression of Slit1, Slit2 and Robo1 in cervical spinal cord was detected by immunofluorescence staining.Results: The scores in the model group were significantly reduced compared to sham-operation group on day 7 (PPPP>0.05). In contrast, significant increase was noticed in the scores in model group, presenting a time-dependent manner. More CST staining fibers could be observed at the degenerative side in the model group compared with that of the sham-operation group on day 21. GAP-43 mRNA expression in the model group showed significant increase compared to that of sham-operation group on day 14 (P=0.015) and 21 days (P=0.002). The expression of GAP-43 protein in model group showed significant increase compared to that of sham-operation group on day 14 (P=0.022) and day 21 (P=0.008), respectively. The expression of Slit1 and Slit2 showed increase on day 14 and day 21, while the expression of Robo1 showed significant decrease in MCAO rats.Conclusion: Up-regulation of Slit1 and Slit2 and the downregulation of Robo1 may be related to the axons of CST midline crossing in spinal cord of MCAO rat during the spontaneous recovery of impaired motor function.

(±)-Pyriindolin (1) with a rare molecular backbone formed by fusing a 2,2′-bipyridine nucleus into a spiro[furan-3,3′-indoline] skeleton, was isolated from the Streptomyces albolongus EA12432. The constitution and the relative configuration of (±)-1 were determined by extensive spectroscopic analyses, 13C calculation and DP4+ probability analysis. The absolute configurations of optically pure (+)-1 and (−)-1 which were obtained after a chiral high performance liquid chromatography (HPLC) separation were further identified by electronic circular dichroism (ECD) calculations. (+)- and (−)-Pyriindolins displayed moderate cytotoxicity against HCT-116 cell line with the half-maximal inhibitory concentration (IC50) values of 2.89 ± 0.17 μmol/L and 4.47 ± 0.26 μmol/L, respectively.

HIV testing is a critical component of effective HIV prevention and care. CDC recommends routine opt-out HIV testing in health care settings for all sexually active persons aged 13-64 years at least once in their lifetime and risk-based testing regardless of age for those who report behaviors associated with HIV acquisition (1). However, recent studies show low HIV testing rates in clinical settings; HIV testing rates at visits to physician offices did not increase during 2009-2016 (2). The objective of the current study is to estimate temporal trends in HIV testing among persons with commercial insurance or Medicaid from 2014 through 2019 and describe their demographic characteristics in 2019. Weighted data from the IBM MarketScan Commercial Claims and Encounters database* (commercial insurance) and from the Centers for Medicare & Medicaid Services (CMS) claims database† (Medicaid) were analyzed to estimate the proportions of persons with commercial insurance or Medicaid who received testing for HIV. Testing rates increased among male and nonpregnant female persons aged ≥13 years with either type of coverage. In 2019, only 4.0% of those with commercial insurance and 5.5% of those with Medicaid received testing for HIV. Testing rates were higher among non-Hispanic Black or African American (Black) persons and Hispanic or Latino (Hispanic) persons. Based on mathematical modeling studies, these annual testing rates would need to increase at least threefold and be sustained over several years (3,4) to achieve the Ending the HIV Epidemic (EHE) in the U.S. initiative goal of ≥95% of persons with HIV being aware of their infection by 2025.§ Interventions need to be implemented to increase routine and risk-based HIV testing in clinical settings to higher levels that can help reduce disparities in HIV diagnoses between Black and Hispanic persons compared with non-Hispanic White (White) persons (5). Increased HIV testing is essential to achieve the goals of the EHE initiative and reduce disparities in HIV diagnoses; public health should partner with health care systems to implement interventions that support increased testing.

Background An excessive postoperative inflammatory response is common after surgery for inflammatory bowel disease (IBD) and may be associated with an increased incidence of postoperative ileus. This study assessed the role of perioperative dexamethasone in postoperative ileus after IBD surgery. Method Patients undergoing elective IBD surgery were randomized to either an intravenous 8-mg dose of dexamethasone (n = 151) or placebo (n = 151) upon induction of anesthesia. The primary outcome was the incidence of prolonged postoperative ileus. Secondary outcomes included incidence of reported nausea or vomiting, time to first passage of flatus and stool, GI-2 recovery, postoperative pain, length of stay, and surgical complications. Results An intention-to-treat analysis revealed that patients who received dexamethasone exhibited a lower incidence of prolonged postoperative ileus (22.5% vs 38.4%; P = 0.003), shorter time to first passage of stool (28 vs 48 h, P Conclusion A single, intravenous 8-mg dose of dexamethasone upon induction of anesthesia reduced the incidence of prolonged postoperative ileus, the intensity of postoperative pain, and shortened the postoperative length of stay for IBD patients undergoing elective surgery. ClinicalTrials.gov: NCT03456752.

Introduction The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several pro‐inflammatory factors. MicroRNA‐233 (miR‐223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR‐223 in dextran sodium sulfate (DSS)‐induced colitis and explore the involvement of the IL‐6/STAT3 pathway in the development of intestinal mucosal inflammation. Materials and Methods Except control (WT) group, male C57BL/6 mice were provided DSS, then treated for with miR‐223 agomir or antagomir including DSS group, DSS + miR‐223 agomir (DSS + A) group, and DSS + miR‐223 antagomir (DSS + AN) group. The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluated by histopathological scoring. The expression of myeloperoxidase (MPO), cytokines and IL‐6/STAT3 pathway‐related proteins were measured. Results miR‐223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS + A group and exacerbated in the DSS + AN group after administration of the miR‐223 agomir and antagomir, respectively. MPO, tumor necrosis factor‐α, IL‐6, and IL‐17 were decreased and IL‐10 was increased in the DSS + A group, but these changes were reversed in the DSS + AN group. Gp130, p‐STAT3, Bcl‐2, and Bcl‐xl in the colon declined in the DSS + A group, but these levels increased in the DSS + AN group. Conclusions The upregulation of miR‐223 by agomir administration alleviated colonic inflammation in a DSS‐induced colitis model, which was likely mediated by inhibiting the production of pro‐inflammatory cytokines via the IL‐6/STAT3 signaling pathway. These findings provide evidence that miR‐223 might have potential therapeutic implications in IBD.

Background Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown. Objective To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database. Design Retrospective cohort study. Setting Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions. Measurements Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments. Results Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance. Limitation The IQVIA database does not capture every prescription nationwide. Conclusion Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion. Primary funding source Centers for Disease Control and Prevention.

Staged surgery (SS) and primary anastomosis (PA) are alternatives to emergency surgery in Crohn's disease (CD). This study aimed to compare postoperative patient outcomes and medical cost of SS and PA for CD emergencies.Consecutive patients with CD undergoing emergency surgery between December 1997 and January 2017 in three centers were included. The PA and SS groups were compared regarding patient outcomes including postoperative complications and surgical recurrence, as well as hospitalization costs.Altogether 96 (39.5%) patients underwent an emergency PA, and 147 (60.5%) underwent an emergency SS. The incidence of intra-abdominal septic complications (IASC) in the PA group was 15.6% compared with 7.5% in the SS group (P = 0.04). The length of hospitalization was longer (32.36 ± 1.76 d vs 19.33 ± 2.36 d, P0.01) and the hospitalization cost was higher in the SS group (USD 15 811.1 ± 1697.1 vs USD 8345.3 ± 919.5, P0.01) than the PA group. SS correlated with a lower surgical recurrence rate than PA (log-rank test, P = 0.04). Presence of diffuse peritonitis, perforating or colonic disease, decision of operation choice made by a senior consultant and more than two concurrent surgical indications were related to the need for SS in emergencies. Localized peritonitis, body mass index (18.5 kg/mSS can be performed with limited IASC and low surgical recurrence rates for surgical emergencies in CD, although it increases hospitalization costs and delays discharge.

Background Although the interaction between gut microbiota and pouchitis after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) has been confirmed, evidence of commensal mycobiota in the etiology of pouchitis is still lacking. This study aimed to investigate the role of fungi in the pathogenesis of pouchitis. Methods Fecal samples were collected from UC patients with or without pouchitis after IPAA. Experimental pouchitis was induced by 5% dextran sulfate sodium for 7 consecutive days in a rat model of IPAA. Fungal dysbiosis was induced by 0.5% fluconazole (Flu), and commensal fungal recognition through dectin-1 was blocked by 5% laminarin. Fecal fungal composition was analyzed using internal transcribed spacer 2 sequencing. Severity of pouchitis and activation of the CARD9-nuclear factor kappa-B pathway was determined among different groups. Results Patients with pouchitis had a lower alpha (α) diversity in mycobiota composition and a higher abundance of Saccharomyces at the genus level compared with those with a normal pouch. In the rat model of pouchitis, Flu treatment decreased fungal burden but induced fungal dysbiosis, characterized by increased α diversity, a decreased relative abundance of Kazachstania, and increased Polythrincium and Saccharomyces. In addition, Flu treatment worsened dextran sulfate sodium pouchitis, as indicated by increased mortality, weight loss, higher histological score, and CD4+ cell infiltration. Laminarin also increased the severity of pouchitis. In the Flu and laminarin groups, the expression of interferon-γ, tumor necrosis factor-α, CARD9, and phosphorylated nuclear factor kappa-B inhibitor alpha was decreased. Conclusions Patients with pouchitis had altered fungal composition. Fungal dysbiosis or recognition deficiency by the host may exacerbate experimental pouchitis. Strategies targeting commensal mycobiota may provide therapeutic potential against pouchitis, especially for antibiotic-refractory patients.

In 2019, the U.S. Department of Health and Human Services launched the Ending the HIV Epidemic: A Plan for America (EHE) initiative to end the U.S. human immunodeficiency virus (HIV) epidemic by 2030. A critical component of the EHE initiative involves early diagnosis of HIV infection, along with prevention of new transmissions, treatment of infections, and response to HIV outbreaks (1). HIV testing is the first step in identifying persons with HIV infection who need to be engaged in treatment and care as well as persons with a negative HIV test result and who are at high risk for infection and can benefit from HIV preexposure prophylaxis (PrEP) and other prevention services. These opportunities are often missed for persons receiving clinical services in ambulatory care settings (2). Data from the 2009-2016 National Ambulatory Medical Care Survey (NAMCS) and 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed to estimate trends in HIV testing at visits by males and nonpregnant females to physician offices, community health centers (CHCs), and emergency departments (EDs) in the United States. HIV tests were performed at 0.63% of 516 million visits to physician offices, 2.65% of 37 million visits to CHCs, and 0.55% of 87 million visits to EDs. The percentage of visits with an HIV test did not increase at visits to physician offices during 2009-2016, increased at visits to CHC physicians during 2009-2014, and increased slightly at visits to EDs during 2009-2017. All adolescents and adults should have at least one HIV test in their lifetime (3). Strategies that reduce clinical barriers to HIV testing (e.g., clinical decision supports that use information in electronic health records [EHRs] to order an HIV test for persons who require one or standing orders for routine opt-out testing) are needed to increase HIV testing at ambulatory care visits.

BACKGROUND Postoperative intra-abdominal septic complications of Crohn's disease substantially increase the healthcare expenditure and prolong hospitalization. OBJECTIVE We aimed to develop and validate a prediction model for intra-abdominal septic complications after bowel resection and primary anastomosis for Crohn's disease. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted in a tertiary center. PATIENTS Data of 949 Crohn's disease-related primary bowel resections and anastomosis from January 2011 to December 2017 were collected. MAIN OUTCOME MEASURES Primary outcomes were prevalence of intra-abdominal septic complications. RESULTS Overall prevalence of intra-abdominal septic complications after Crohn's disease surgery was 11.6%. Predictors included preoperative C-reactive protein level ≥40 mg/L (OR = 3.545), preoperative glucocorticoids (OR = 1.829) and infliximab use (OR = 3.365), upper GI involvement (OR = 2.072), and hypoalbuminemia (albumin level

In order to discover structurally new and bioactive compounds from marine life, we studied the secondary metabolites of the marine-derived fungi associated with a marine sponge (XS-3) from the Xisha islands. As a result, 4-O-methylcandidusin A (1), a new p-terphenyl alcohol, along with nine known analogs (2–10), were isolated and identified from the marine sponge-derived fungus Aspergillus candidus OUCMDZ-1051. The structures of these compounds were determined by analyzing spectroscopic data, especially 1D and 2D NMR. The new compound 1 selectively inhibited the growth of the MDA-MB-468, BT474 and A431 human cancer cell lines with the IC50 values of 1.84, 6.05 and 0.98 μmol/L, respectively. Compound 1 also displayed a selective antimicrobial activity against Escherichia coli with an MIC value of 27.3 μmol/L. The results indicated 4-O-methylcandidusin A (1) as a potential lead in the new drug discovery for triple negative breast cancer, invasive ductal breast cancer and epidermoid cancer. The antimicrobial metabolites also evidenced a clue for chemical defense of sponges by their associated microorganisms.

Objective: Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) use as HIV preexposure prophylaxis (PrEP) is monitored by identifying TDF/FTC prescriptions from pharmacy databases and applying diagnosis codes and antiretroviral data to algorithms that exclude TDF/FTC prescribed for HIV postexposure prophylaxis (PEP), HIV treatment, and hepatitis B virus (HBV) treatment. We evaluated the accuracy of 3 algorithms used by the Centers for Disease Control and Prevention (CDC), Gilead Sciences, and the New York State Department of Health (NYSDOH) using a reference population in Bronx, New York. Methods: We extracted diagnosis codes and data on all antiretroviral prescriptions other than TDF/FTC from an electronic health record database for persons aged ≥16 prescribed TDF/FTC during July 2016–June 2018 at Montefiore Medical Center. We reviewed medical records to classify the true indication of first TDF/FTC use as PrEP, PEP, HIV treatment, or HBV treatment. We applied each algorithm to the reference population and compared the results with the medical record review. Results: Of 2862 patients included in the analysis, 694 used PrEP, 748 used PEP, 1407 received HIV treatment, and 13 received HBV treatment. The algorithms had high specificity (range: 98.4%-99.0%), but the sensitivity of the CDC algorithm using a PEP definition of TDF/FTC prescriptions ≤30 days was lower (80.3%) than the sensitivity of the algorithms developed by Gilead Sciences (94.7%) or NYSDOH (96.1%). Defining PEP as TDF/FTC prescriptions ≤28 days improved CDC algorithm performance (sensitivity, 95.8%; specificity, 98.8%). Conclusions: Adopting the definition of PEP as ≤28 days of TDF/FTC in the CDC algorithm should improve the accuracy of national PrEP surveillance.

BackgroundWe assessed prevalence of testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection among persons who inject drugs (PWID).MethodsUsing a nationwide health insurance database for claims paid during 2010–2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and we used multivariate logistic regression models to assess demographic and clinical factors associated with testing.ResultsOf 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) were tested for HCV infections. Missed opportunities were independently associated with being male (odds ratios [ORs]: HIV, 0.50 [95% confidence interval {CI}, 0.49–0.50], P < .001; HCV, 0.66 [95% CI, 0.65–0.72], P < .001), rural residence (ORs: HIV, 0.67 [95% CI, 0.65–0.69], P < .001; HCV, 0.75 [95% CI, 0.73–0.77], P < .001), and receiving services for skin infections or endocarditis (adjusted ORs: HIV, 0.91 [95% CI, 0.87–0.95], P < .001; HCV, 0.90 [95% CI, 0.86–0.95], P < .001).ConclusionsApproximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use.

Endoscopy remains the gold standard for evaluating postoperative recurrence in Crohn's disease. Timely therapy adjustment according to endoscopic findings can improve long-term outcomes.We aimed to determine the characteristics, clinical values, and safety of the endoscopic evaluation at 1 month after surgery.This was a prospective observational study.This study was conducted in a tertiary referral hospital.Patients with Crohn's disease undergoing ileocolic resection between January 2016 and November 2018 were included.The first postoperative ileocolonoscopy was performed at 4-5 weeks after surgery.The primary outcome was postoperative recurrence within 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors.Among 84 ileocolonoscopies at 4-5 weeks, no endoscopic complication occurred. The main endoscopic findings at the first evaluation were anastomotic circumferential ulcers (10, 11.9%), anastomotic scattered ulcers (35, 41.7%), ulcers in the neoterminal ileum (16, 19.0%), edema in anastomosis (50, 59.5%), mild narrowing in anastomosis (7, 8.3%), and mild narrowing in neoterminal ileum (3, 3.6%). Anastomotic scattered ulcers were associated with future postoperative recurrence (OR, 2.532 (95% CI, 1.02-6.32), p = 0.046). Fecal calprotectin150 ug/g on postoperative day 14 could predict anastomotic scattered ulcers (OR' 2.91 (95% CI, 1.31-7.47), p = 0.027). The modified Rutgeerts score was used to define endoscopic findings: i0, 37 (44.0%); i1, 4 (4.8%); i2a, 29 (34.5%); i2b, 11 (13.1%); i3, 0; i4, 3 (3.6%). Score ≥i2a were associated with future postoperative recurrence (OR, 3.17 (95% CI, 1.22-8.27), p = 0.018). No factor was associated with a Rutgeerts score of ≥i2a at the first endoscopic evaluation.This was a single-center study with a small cohort of patients.Endoscopic evaluation at 1 month after surgery in CD was safe. Anastomotic scattered ulcers occurred in nearly half of patients and were associated with future postoperative recurrence. See Video Abstract at http://links.lww.com/DCR/B760.LA EVALUACIÓN ENDOSCÓPICA A UN MES DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PARA LA ENFERMEDAD DE CROHN, PREDICE FUTURA RECURRENCIA POSOPERATORIA Y ES SEGURAANTECEDENTES:La endoscopia sigue siendo el estándar de oro para evaluar la recurrencia posoperatoria en la enfermedad de Crohn (EC). El ajuste oportuno en la terapia de acuerdo con los hallazgos endoscópicos, puede mejorar los resultados a largo plazo.OBJETIVO:Determinar las características, valores clínicos y seguridad de la evaluación endoscópica, al mes de la cirugía.DISEÑO:Estudio observacional prospectivo.ENTORNO CLINICO:El estudio se llevó a cabo en un hospital de referencia terciario.PACIENTES:Se incluyeron pacientes con EC sometidos a resección ileocólica entre enero de 2016 y noviembre de 2018.INTERVENCIONES:La primera ileocolonoscopia posoperatoria se realizó a las 4-5 semanas posteriores a la cirugía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia posoperatoria dentro de los 12 meses posteriores a la cirugía. Se realizaron análisis univariados y multivariados para identificar factores de riesgo.RESULTADOS:Entre 84 ileocolonoscopias a las 4-5 semanas, no ocurrió ninguna complicación endoscópica. Los principales hallazgos endoscópicos en la primera evaluación, fueron úlceras anastomóticas circunferenciales (10, 11,9%), úlceras anastomóticas dispersas (35, 41,7%), úlceras en el íleon neo-terminal (16, 19,0%), edema en la anastomosis (50, 59,5%), estrechamiento leve en la anastomosis (7, 8,3%) y estrechamiento leve en el íleon neo-terminal (3, 3,6%). Las úlceras anastomóticas dispersas se asociaron con recurrencia posoperatoria futura (OR, 2,532 (95% CI, 1,02-6,32), p = 0,046). La calprotectina fecal en el post d 14150 ug / g podría predecir úlceras anastomóticas dispersas (OR' 2,91 (95% CI, 1,31-7,47), p = 0,027). Se utilizó la puntuación de Rutgeerts modificada para definir los hallazgos endoscópicos: i0, 37 (44,0%); i1, 4 (4,8%); i2a, 29 (34,5%); i2b, 11 (13,1%); i3, 0; i4, 3 (3,6%). La puntuación ≥i2a se asoció con recurrencia posoperatoria futura (OR, 3,17 (95% CI, 1,22-8,27), p = 0,018). Ningún factor se asoció con ≥i2a en la primera endoscopia.LIMITACIONES:Estudio de un solo centro con una pequeña cohorte de pacientes.CONCLUSIONES:La evaluación endoscópica al mes de la cirugía en EC, fue segura. Se produjeron úlceras anastomóticas dispersas en casi la mitad de los pacientes y se asociaron con una futura recurrencia posoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B760. (Traducción - Dr. Fidel Ruiz Healy).

Objective: To evaluate the influence of the abdominal incision length on the gastrointestinal function recovery post-operatively.Background: Gut motility recovers more quickly after the minimally invasive laparoscopic surgery compared than after the traditional open surgery; however, whether the minimal abdominal incision contributes to the faster gut motility recovery is controversial and lacks solid clinical evidence.Methods: A registry-based secondary cohort analysis was conducted to evaluate the association between the abdominal incision length and gut motility recovery post-operatively based on a multicenter, prospective, and observational study of the prolonged post-operative ileus (PPOI) incidence and the risk factors in the patients with the major abdominal surgery. The incision length, in the centimeters, was the exposure. The primary outcome measures were the PPOI incidence and its association with the incision length. The secondary outcome included the days to the first passage of flatus and the days to the first passage of stool.Results: Overall, 1,840 patients, including 287 (15.7%) patients with the PPOI, were recruited. The PPOI incidence was 17.6% and 13.3% in the long-incision (>18 cm) and short-incision patients ( ≤ 18 cm), respectively. The incidence of the PPOI increased by 1.1% (1.0–1.1) by each centimeter increment of the incision length after adjusting for the confounding factors. In comparison to the short-incision patients, the long-incision patients had prolonged passage of stool (4.46 vs. 4.95 days, p < 0.001). Each centimeter increment of the incision length contributed to a 2% increased risk of delay in the first bowel movement [hazard ratio (HR) 0.980 (0.967, 0.994)].Conclusion: A long abdominal incision length independently contributed to the prolonged gut function recovery post-operatively mainly by delaying the time to the first bowel movement, but not influencing the time to first passage of flatus.

Postoperative intra-abdominal septic complications in patients with Crohn's disease undergoing intestinal resection and anastomosis are frequent and difficult to manage.This study sought to explore the value of preoperative CT enterography to predict intra-abdominal septic complications.This was a retrospective and prospective observational study.This study was conducted in a tertiary referral hospital.Patients with Crohn's disease undergoing primary intestinal resection were enrolled in our study.The CT enterography severity index was calculated and its ability to predict intra-abdominal septic complications evaluated by multivariate analyses. A prospective study was then performed to assess the reliability of this CT enterography index.The incidence of postoperative intra-abdominal septic complications in patients undergoing a 1-stage procedure was significantly higher than those undergoing a 2-stage procedure (3/103 vs 24/241; 2.9% vs 10.0%; p = 0.026). A multivariate analysis identified 5 CT enterography parameters, including mesenteric fibrofatty proliferation, intra-abdominal abscess or phlegmon, intestinal fistula, peritoneal effusion, and intestinal dilatation with stricture to be independent predictors of intra-abdominal septic complications (p0.001). A nomogram model based on these 5 parameters was constructed. A receiver operating characteristic analysis identified a CT enterography nomogram score cutoff of 175 as a predictor of intra-abdominal septic complications with a sensitivity of 83.3% and a specificity of 85.3%. In the prospective study, those patients with a CT enterography nomogram score175 were assigned to the 2-stage group, which resulted in a similar intra-abdominal septic complication incidence in those undergoing intestinal resection with or without anastomosis (2/82 vs 2/34; p = 0.355).This study was limited by its single-center scope.Preoperative CT enterography findings may predict postoperative outcomes and help determine surgical approach in Crohn's disease. Patients with worse intra-abdominal findings confirmed by CT enterography may benefit from stoma creation after intestinal resection. See Video Abstract at http://links.lww.com/DCR/B588.ANTECEDENTES:Las complicaciones sépticas intra-abdominales postoperatorias en pacientes con enfermedad de Crohn sometidos a resección intestinal y anastomosis son frecuentes y difíciles de manejar.OBJETIVO:Este estudio buscó explorar el valor del índice enterográfico por tomografía computada en el pré-operatorio y así poder predecir futuras complicaciones sépticas intra-abdominales.DISEÑO:Estudio observacional retro-prospectivo.AJUSTE:Investigación realizada en un hospital de referencia terciaria.PACIENTES:Se incluyeron en nuestro estudio pacientes con enfermedad de Crohn sometidos a una resección intestinal primaria.PRINCIPALES MEDIDAS DE RESULTADO:Se calculó el índice de gravedad de la enterografía por tomografía axial computada y se evaluó su capacidad para predecir las complicaciones sépticas intra-abdominales mediante un análisis multivariado. Luego se realizó un estudio prospectivo para evaluar la confiabilidad del índice enterográfico por tomografía axial computada.RESULTADOS:La incidencia de complicaciones sépticas intra-abdominales postoperatorias en pacientes sometidos a un procedimiento de un solo tiempo fue significativamente mayor que aquellos sometidos a un procedimiento de dos tiempos (3/103 frente a 24/241; 2,9% frente a 10,0%; p = 0,026). El análisis multivariado identificó cinco parámetros enterográficos por tomografía axial computada, incluidos la proliferación fibrograsa mesentérica, el absceso o flegmón intra-abdominal, la fístula entérica, el derrame peritoneal y la dilatación intestinal debido a estenosis como predictores independientes de complicaciones sépticas intra-abdominales (p0,001). Se construyó un modelo de Nomograma basado en estos cinco parámetros. Un análisis de las características operatorias del receptor identificó una puntuación de cohortes del nomograma de la enterografía por tomografía axial computada de 175 como predictor de complicaciones sépticas intra-abdominales con una sensibilidad del 83,3% y una especificidad del 85,3%. En el estudio prospectivo, los pacientes con puntuación de nomograma enterográfico por tomografía axial computada superior a 175 fueron asignados al grupo en dos tiempos, lo que resultó en una incidencia similar de complicaciones sépticas intra-abdominales en aquellos sometidos a resección intestinal con o sin anastomosis (2/82 vs. 2/34; p = 0,355).LIMITACIONES:Este estudio estuvo limitado por su alcance unicéntrico.CONCLUSIÓN:Los hallazgos enterográficos por tomografía axial computada pré-operatoria pueden predecir ciertos resultados postoperatorios y ayudar a determinar el abordaje quirúrgico en la enfermedad de Crohn. Los pacientes con peores hallazgos intra-abdominales confirmados por enterografía en la tomografía axial computada podrían beneficiarse de la creación de un estoma después de la resección intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B588. (Traducción-Dr Xavier Delgadillo).

Aim Crohn's disease affects the entire gastrointestinal tract and is accompanied by changes in disease location and behaviour. We aimed to analyse changes and the factors in patients with Crohn's disease undergoing intestinal repeated-resection. Methods We included and retrospectively analyzed patients with Crohn's disease who received ≥2 bowel surgeries from a tertiary inflammatory bowel disease centre from January 2008 to December 2019. The Montreal classification was used to describe the disease site and behaviour. Factors were assessed by univariate and multivariate analysis. Results A total of 339 patients were included of whom 94 patients received ≥3 bowel resections. The median patient's age at the second and third surgery was 36.4 and 39.6, respectively. Repeated-resection most commonly occurred in the original surgical site. However, disease behaviour progressed with the number of surgical interventions and disease duration, especially for patients with B1 phenotype. Patients with L1 Crohn's disease at a primary resection that progressed to L2 Crohn's disease at a second surgical resection required a resection earlier than patients whose disease remained in L1 or progressed to L3 Crohn's disease. Multivariate analysis showed that history of appendectomy was a predictor of progression from L1 to L3 Crohn's disease at a second surgical resection, while treatment with azathioprine (AZA) may be a protective factor that abated the risk of progression from L1 to L3 Crohn's disease. Conclusion The original resection site is the most common location for recurrence in patients with Crohn's disease, but disease behaviour progresses with the number of surgeries and disease duration. L1 Crohn's disease patients with a history of appendectomy have a higher risk to progress to L3 Crohn's disease at a second surgical resection, while the AZA may be a protective factor that reduces the risk of progression from L1 to L3.

Summary Background & aims Exclusive enteral nutrition (EEN) as a primary therapy is safe and effective for inducing the clinical remission of active luminal Crohn's disease (CD). Whether isolated colonic involvement affects the efficacy of EEN is controversial. We aimed to identify the influence of isolated colonic CD on the efficacy of EEN and to determine other potential predictors of the response to induction therapy with EEN in adult patients with CD. Methods Data for adult CD patients treated with EEN as an induction therapy at our centre from January 1, 2014, to May 31, 2017, were reviewed. Eligible patients were divided into an isolated colonic Crohn's disease (cCD) group and a non-isolated colonic Crohn's disease (non-cCD) group according to the disease location. The rates of clinical remission and inflammatory and nutritional serum markers were compared between the groups. Possible relationships between isolated colonic involvement or other potential factors and the efficacy of EEN were assessed by univariate and multivariate analyses. The propensity score matching method was used to confirm the results. Results Overall, 241 patients were included in the analysis: 52 patients in the cCD group and 189 patients in the non-cCD group. The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2–6.23], P = 0.016). Additionally, the lean body mass index (LBMI) before treatment was associated with the efficacy of EEN (OR = 0.636; [CI] 95% = [0.444–0.912], P = 0.014). These associations were confirmed using the propensity score model. For patients with isolated colonic CD, multivariate analysis showed that pancolitis (OR = 16.7; [CI] 95% = [1.074–260.5], P = 0.044) was another independent factor for the efficacy of EEN. Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group. Conclusions Isolated colonic CD showed a reduced response to induction therapy with EEN compared with ileal or ileocolonic disease in adult patients. Patients with isolated colonic CD required more time to benefit from EEN therapy compared with patients with non-colonic CD. Additionally, LBMI before treatment was associated with the efficacy of EEN.

A site-specific drug delivery system of anticancer agents has been delveloped to enhance the therapeutic efficacy and reduce toxicity to the normal tissue. Semi-synthetic andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide) is one of the potential natural anticancer compounds against many types of cancer including colorectal cancer cells. However, the clinical applications of this compound are limited because of low water solubility and lack of suitable delivery carriers. This study aimed to increase the aqueous solubility and improve the anticancer efficacy of 3A.1 via active targeting approaches. In this study, 3A.1 was loaded into the polymeric micelles self-assembled from N-naphthyl-N,O-succinyl chitosan (NSC). The micelles were conjugated with folate moiety (Fol-NSC) for targeting to the cancer cells. All of the 3A.1-loaded micelles were prepared by dropping method, and the physicochemical properties (size, charge, morphology, encapsulating efficiency, loading capacity), in vitro release behavior and in vitro anticancer activities against HT29 colorectal cancer cells were investigated. The 3A.1-loaded micelles were successfully formulated by dropping method using NSC or Fol-NSC. The micelles loaded with 40% initial 3A.1 showed the maximum encapsulating efficiency and loading capacity. The micelles were in the nanometer range, having a negative surface charge and a spherical structure. The colon site-specific release of the 3A.1 from the 3A.1-loaded micelles was obtained. The release of 3A.1 from the Fol-NSC micelles was slower than that from the NSC micelles. Moreover, the Fol-NSC micelles exhibited superior anticancer efficacy than that of the NSC micelles and free 3A.1. In conclusions, the 3A.1-loaded Fol-NSC micelles developed in the present study had suitable physicochemical properties. These nanocarriers may be a potential delivery system for targeted delivery of the 3A.1 to colorectal cancer cells.

The rate of postoperative ileus following stoma closure is high in patients with Crohn’s disease and temporary enterostomy. To evaluate the effect of chyme reinfusion on postoperative outcomes including ileus in these patients. Patients were screened from January 2012 to December 2017 and divided into chyme reinfusion group (n = 33) and non-chyme reinfusion group (n = 84). The following 30-day postoperative outcomes were evaluated. Univariate and multivariate analyses and propensity score matching were performed to identify risk factors for these postoperative outcomes. The incidence of postoperative ileus was significantly lower in the chyme reinfusion than in non-chyme reinfusion group, which had been confirmed by the results after matching (3/26 vs 11/26, p = 0.012). The rate of postoperative diarrhea was significantly lower in the chyme reinfusion group compared with non-chyme reinfusion group, whereas the difference was not significant after matching (2/26 vs 6/26, p = 0.191). Additionally, the postoperative length of stay was significantly shorter in the chyme reinfusion than in non-chyme reinfusion group before and after propensity score matching. In the multivariate analysis, chyme reinfusion was an independent protective factor for postoperative ileus (odds ratio 0.218; 95% confidence interval 0.05–0.95; p = 0.042) and for postoperative length of stay (coefficient − 0.191; 95% confidence interval − 0.350 to − 0.032, p = 0.019). Chyme reinfusion was associated with lower rate of postoperative ileus and shorter length of stay following stoma closure in Crohn’s patients with temporary ileostomy. Further randomized clinical trial between patients with or without chyme reinfusion was needed to confirm these conclusions.

Objective In China, patients generally seek health care at high-level hospitals, which is leading to escalating medical costs and overloaded hospitals. Some studies have suggested that the health system is an important factor influencing individuals' health care-seeking behaviour; however, this association has not been studied in much depth. We therefore examined the impact of the health system (in terms of the interaction between health insurance reimbursement and health workforce) on health care-seeking behaviour. Methods Drawing on national survey data from 2008 and 2013, we linked individual-level data on choice of health care providers (our index of health care-seeking behaviour) with county-level data on the health workforce and health insurance. We then constructed a multilevel multinomial logistic model to examine the impacts of health insurance reimbursement (indexed as average reimbursement rate [ARR]) and the health workforce (number of registered physicians per 1000 population) at county hospitals and primary health care institutions (PHCs) on choice of inpatient care providers. Results Increases in ARR at county hospitals were associated with a greater probability of visiting such hospitals (relative risk ratio [RRR] = 1.23), and this positive impact was even greater in county hospitals with higher physician densities (RRR = 2.76). Greater ARR in PHCs was associated with a 73% lower probability of visiting municipal- and higher-level hospitals; increasing ARR was associated with an even lower probability when physician density in PHCs was considered (RRR = 0.09). Conclusion Increases in the health insurance reimbursement and health workforce are necessary to improve health care access and thereby health care-seeking behaviour. Thus, comprehensive health system reform is necessary.

Background Conservative therapy for Crohn’s disease (CD)-related acute bowel obstruction is essential to avoid emergent surgery. The present study aimed to evaluate the efficacy of using a long intestinal decompression tube (LT) in treatment of CD with acute intestinal obstruction. Methods This is a prospective observational study. Comparative analysis was performed in CD patients treated with LT (the LT group) and nasogastric tube (the GT group). The primary outcome was the avoidance of emergent surgery. Additionally, predictive factors for failure of decompression and subsequent surgery were investigated. Results There were 27 and 42 CD patients treated with LT and GT, respectively, in emergent situations. Twelve (44.4%) patients using LT were managed conservatively without laparotomy, while only nine (21.4%) patients in the GT group were spared from emergent surgery (P 500 mL were predictors of unavoidable surgery (both P 0.05). Conclusions Endoscopic placement of LT could improve the emergent status in CD patients with acute bowel obstruction. The drainage output and changes in C-reactive protein after intubation could serve as practical predictive indices for subsequent surgery. Compared to traditional GT decompression, LT decompression was associated with fewer short-term complications and did not appear to affect long-term recurrence.

BACKGROUND The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. OBJECTIVE We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. DESIGN This was a prospective observational study. SETTINGS This study was conducted in a tertiary referral hospital. PATIENTS One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. MAIN OUTCOME MEASURES Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. RESULTS The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 μg/g. LIMITATIONS This is a single-center trial with a limited cohort of patients. CONCLUSIONS The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.

Citridones E–G (1–3), three new phenylpyridone derivatives together with two known curvularins (4 and 5) were isolated from the solid culture of the endophytic fungus Penicillium sumatrense GZWMJZ-313 in Garcinia multiflora. The structures of new compounds were determined in the light of spectroscopic data, X-ray and ECD calculation. Compounds 1 and 3 are racemates, while compound 2 is optically pure. Compounds 1 and 4 showed antibacterial and antifungal activities against Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli and Candida albicans with MIC values ranging from 8 μg/mL to 64 μg/mL.

Caerulomycins are a family of natural alkaloids featuring a 2,2′-bipyridine nucleus. Since the first example of caerulomycins, caerulomycin A from Streptomyces caeruleus, was reported in 1959, there have been 34 natural caerulomycins from microorganisms reported. The unique structure of caerulomycins and their potential bioactivity, including antifungal activity, cytotoxicity, and immunosuppression, have attracted the interest of both chemists and biologists. Herein, we report 8 new caerulomycins (19–22 and 39–42) as well as 14 known analogues (1–3, 6–9, 16, 18, 24, 25, 27, 29, and 31) from wild-type and mutant Actinoalloteichus cyanogriseus WH1-2216-6. The structures including the absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray single crystal diffraction, 1-phenyl-3-methyl-5-pyrazolone (PMP)-labeling HPLC analysis, Mosher's method and quantum electronic circular dichroism (ECD) calculation. The cytotoxicity of caerulomycins 1–42 and some previously reported analogues was assayed against six human tumor cell lines and a human normal liver cell line, L-02. Compounds 1, 2, 5, 13, 18, 27, and 39 exhibited moderate to strong cytotoxicity against the tumor cells with IC50 values ranging from 0.1 to 50 μM. The structure and activity relationships (SARs) are also discussed. In addition, the caerulomycin glycosides (29, 34, and 39) showed effective selectivity against HCT-116 cells with low toxicity toward the normal L-02 cell line, indicating their potential use as lead compounds for antitumor drugs.

Crohn's disease (CD)-associated adherent invasive Escherichia coli (AIEC) has been implicated as a causative or contributory factor in CD pathology. MicroRNA let-7b/Toll-like receptor 4 (TLR-4) signaling pathways may play an important role in microbiota-mucosa interactions. We aimed to investigate whether AIEC influences IECs' function of expressing TLR4, and the potential role of let-7b in regulating AIEC induced gut inflammation. Wild type (WT) and interleukin-10 knockout (IL-10 KO) mice in specific pathogen free (SPF) housing were infected by AIEC LF82, and IL-10 KO mice were treated with pre-let7b or anti-let-7b. Besides, T84 cells were infected by AIEC LF82 or E. coli K-12, and treated with let-7b mimics or inhibitor. let-7b/TLR4 signaling pathway was investigated and the therapeutic effects of let-7b treatment on colitis in IL-10-mice and on cytokines release in T84 were assessed. We found AIEC elicited/exacerbated colitis in WT/IL-10 KO mice, and promoted proinflammatory cytokines release in T84 cells that correlated with increased TLR4 expression and decreased let-7b. Overexpression of let-7b significantly ameliorated the severity of colitis in AIEC infected IL-10 KO mice, and reduced secretion of cytokines in AIEC-infected T84 cells via regulating TLR4 expression. Besides, overexpression of TLR4 caused by inhibition of let-7b led to increased proinflammatory cytokines release in K-12 infected T84 cells. These results suggest AIEC instigates excessive mucosal immune response against gut microbiota via let-7b/TLR4 signaling pathway. Let-7b may be a potential therapeutic target of CD, especially for CD with AIEC infection.

Objective The Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project created collaboratives of health departments, community-based organizations, and clinical partners to improve HIV prevention services for men who have sex with men (MSM) and transgender women (TGW) of color. We administered an online survey from September 2018 through February 2019 to assess the collaboratives. Methods We used a Likert scale to measure agreement on collaborative characteristics. We used Fisher exact tests to compare success ratings by health department employment and funding status. We created a radar chart to compare the percentage agreement on key characteristics of the most and least successful collaboratives. We used a general inductive approach in the qualitative analysis of open-ended question responses. Results Of 262 survey recipients, 133 responded (51%); 49 (37%) respondents were from health departments. Most respondents (≥70%) agreed that their collaborative is diverse, cooperates, meets regularly, has realistic goals, has effective leadership, and has effective communication. Most respondents (87%) rated their collaborative as successful in implementing HIV prevention services for MSM and TGW of color. Comparison of the most and least successful collaborative found the greatest difference in respondent agreement in the presence of effective leadership, communication, and adequate resources. The most commonly cited challenge in the open-ended questions was inadequate resources. The most commonly cited success was increased provision of services, particularly preexposure prophylaxis. Conclusions Community collaboratives were considered successful by most collaborative members and may be an effective part of HIV prevention strategies.

Background: The coronavirus disease 2019 (COVID-19) pandemic has lasted much longer than an influenza season, but the main signs, symptoms, and some imaging findings are similar in COVID-19 and influenza patients. The aim of the current study was to construct an accurate and robust model for initial screening and differential diagnosis of COVID-19 and influenza A.Methods: All patients in the study were diagnosed at Fuyang No. 2 People's Hospital, and they included 151 with COVID-19 and 155 with influenza A. The patients were randomly assigned to training set or a testing set at a 4:1 ratio. Predictor variables were selected based on importance, assessed by random forest algorithms, and analyzed to develop classification and regression tree models.Results: In the optimal model A, the best single predictor of COVID-19 patients was a normal or high level of low-density lipoprotein cholesterol, followed by low level of creatine kinase, then the presence of Conclusions: The two models provide clinicians with a rapid triage tool. The optimal model can be used to developed countries/regions and major hospitals, and the suboptimal model can be used in underdeveloped regions and small hospitals.

One new (1) and fifteen known (2–16) p-terphenyls were isolated from a solid culture of the endophytic fungus Aspergillus sp. GZWMJZ-055 by adding the leaves of its host Eucommia ulmoides. Furthermore, nine p-terphenyls (17–25) were synthesized from the main compounds (5–7), among which derivatives 18, 19, 21, 22, and 25 are new p-terphenyls. Compounds 15 and 16 were also, respectively, synthesized from compounds 6 and 7 by oxidative cyclization of air in the presence of silica gel. These p-terphenyls especially those with 4,2′,4″-trihydroxy (4–7, 20, 21) or 4, 4″-dihydroxy-1,2,1′,2′-furan (15, 16) substituted nucleus, exhibited significant antioxidant and α-glucosidase inhibitory activities and lower cytotoxicity to caco-2 cells. The results indicated their potential use as lead compounds or dietary supplements for treating or preventing the diabetes.

PRAS40 (Prolin-rich Akt substrate of 40 kDa) is a critical protein, which directly connects PI3K/Akt and mTORC1 pathway. It plays an indispensable role in the development of various diseases. However, the relationship between PRAS40 and head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, our study indicated that high expression of PRAS40 mRNA is a favorable prognostic factor in HNSCC patients by analyzing 498 clinical and mRNA data. Moreover, we confirmed that CRISPR/Cas9 induced PRAS40-knockout would promote colony formation, cell migration, and invasion in several HNSCC cell lines. RNA-seq was employed to investigate the further possible mechanisms involving the above regulations by PRAS40 in HNSCC cells. The molecular landscape contributed by 253 differentially expressed mRNA after PRAS40-knockout was enriched in TGF-beta, PI3K-Akt, P53, mTOR, NF-κB signaling pathway. Partial molecular alternations within these pathways were validated by qPCR or Western blotting. Besides, we found that high expression of PRAS40 in HNSC patients would present more CD8+ T and T follicular helper cells, but less Th17 cells than the patients with low expression of PRAS40. The altered molecular pathways and tumor-infiltrating immune cells might associate with the mechanism of PRAS40 being a suppressor in HNSCC cells, which would provide a potential prognostic predictor and therapeutic target in HNSCC patients.

Background Crohn’s disease [CD] is a chronic, relapsing and incurable inflammatory disorder. Micro RNAs [miRNAs], which modulate gene expression by binding to mRNAs, may make significant contributions to understanding the complex pathobiology and aetiology of CD. This study aimed to investigate the therapeutic role and mechanism of miR-130a-3p in CD. Methods Differentially expressed miRNAs in colon tissues of CD patients and normal controls [NCs] were screened using an miRNA microarray and then validated by quantitative reverse transcriptase-PCR [qRT-PCR]. The functional role of miR-130a-3p in the pathogenesis of CD was then demonstrated by in vitro and in vivo studies. The target genes of miR-130a-3p and the associated signalling pathways were identified using bioinformatics analysis and experimental verification of the interactions between the target predicted by the algorithms and dysregulated mRNAs. The therapeutic role of miR-130a-3p in trinitro-benzene-sulfonic acid [TNBS]-induced colitis models was further investigated. Results Our data demonstrated that miR-130a-3p is the most significantly upregulated miRNA and that miR-130a knockout significantly protects mice against TNBS-induced colitis. Gain- and loss-of-function studies indicated that miR-130a-3p promotes CD development by targeting ATG16L1 via the NF-κB pathway. Furthermore, an miR-130a-3p inhibitor significantly suppressed NLRP3 inflammasome activity by inducing autophagy in a mouse macrophage cell line [RAW264.7]. Therapeutically, an miR-130a-3p inhibitor effectively ameliorated the severity of TNBS-induced colitis. Conclusion Our study reveals that miR-130a-3p promotes CD progression via the ATG16L1/NF-κB pathway and serves as a potential preclinical therapeutic target in CD.

Background People bypass primary healthcare (PHC) institutions to seek expensive healthcare at high-level hospitals, leading to escalating medical costs and inefficient use of resources. In 2009, China launched nationwide synergic policies on primary care strengthening, to tackle access to healthcare and financial protection. This study aimed to assess the impact of the two policy areas, health insurance and health workforce, on healthcare seeking behavior. Methods Drawing on national survey data before (2008) and after (2013) the policies, we linked individual-level data on healthcare-seeking behavior with county-level data on health workforce and health insurance. We constructed a multilevel zero-inflated negative binomial regression to examine the impacts of average reimbursement rate (ARR) of health insurance and the density of registered physicians on outpatient/inpatient visits, and multilevel multinomial logistic regression for the impacts on choice of outpatient/inpatient care providers. Results Although the increase in health insurance ARR and physician density have positive impacts on individuals’ healthcare use, their impacts might be weakened during 2008 and 2013, and the negative impacts of investment of those in PHC institutions on likelihood of visiting hospitals was larger. The negative impacts of ARR at PHC institutions on likelihood of visiting county-, municipal- and higher-level hospitals in 2013 was 28 percentage points, 66 percentage points and 33 percentage points larger than these in 2008. Conclusions Primary care strengthening requires synergic policies. Effective mechanisms for coordination across multisectoral actions are necessities for deepening those policies to ensure efficient delivery of healthcare without experiencing financial risks.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation-targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation-responsive metal-organic framework material (Ce-MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce-MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce-MOF@PSS delivery system exhibits excellent inflammation-targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. Accordingly, by targeting intestinal inflammation, increasing local drug concentrations, scavenging ROS, reducing systemic exposure, and exhibiting excellent safety profiles, it is considered that the Ce-MOF drug delivery platform can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

The link between differences in molecular expression and survival among advanced laryngeal (LSCC) and hypopharyngeal squamous carcinoma (HPSCC) remains unclear. Here, we applied the Surveillance, Epidemiology, and End Results (SEER) program, Isobaric tag for relative and absolute quantitation (iTRAQ) with Liquid chromatography-mass spectrometry (LC–MS/MS) proteomics data and The Cancer Genome Atlas (TCGA) related data to discover the possible disparities between HPSCC and LSCC. Our results showed a significantly worse 5-year overall-survival in HPSCC compared with LSCC before and after adjusting for clinical parameters. 240 differentially expressed proteins were enriched in molecular networks of cytoskeleton remodeling and antigen presentation. Moreover, HPSCC consisted of less T-central-memory cells, T-follicular-helper cells, TGF-β response, and CD4 + T memory resting cells, but more wound healing than LSCC. Furthermore, 9 mRNAs expression were significantly and independently correlated to overall survival in 126 HPSCC and LSCC patients, which was further validated in another cohort of head and neck cancers. These findings support that Immunity signatures as well as pathway networks that include cytoskeleton remodeling and antigen presentation may contribute to the observed differences in survival between HPSCC and LSCC.