Anti-TNF and immunosuppressive combination therapy is preferential to inducing clinical remission in patients with active inflammatory bowel disease: A systemic review and meta-analysis.

OBJECTIVE: To compare the efficacy and safety of a combination therapy of biologics and immunosuppressants with biological monotherapy in inflammatory bowel disease (IBD) in a systematic review and meta-analysis. METHODS: Eligible randomized controlled trials (RCTs) on the comparison of the efficacy and safety of biologics and immunomodulators with biological monotherapy were identified from the EMBASE, PubMed and the Cochrane Library databases published up to 1 May 2020. Raw data were extracted, pooled relative risk (RR) and 95% confidence interval (CI) was calculated, the fixed-effect and inverse variance models were used. Funnel plots were performed to analyze publication bias. RESULTS: Twelve RCTs were eligible for analysis. Overall, there was statistically a benefit for combination treatment over biologic monotherapy (IFX/ADA) in inducing clinical remission and preventing relapse in patients with IBD (RR 0.89, 95% CI 0.80-0.98). Moreover, the combination therapy was superior to biological monotherapy for active CD (RR 0.83, 95% CI 0.73-0.94). Also, there were significant benefits for combination therapy in the subgroup treated with infliximab (IFX) (RR 0.83, 95% CI 0.70-0.97). CONCLUSIONS: Combination therapy has slight benefits in inducing clinical remission in active CD compared with biological monotherapy. Patients with IBD who receive therapy with IFX and immunomodulator also have a mild advantage in comparison with those treated with IFX monotherapy.

Folic acid-modified nonionic surfactant vesicles for gambogenic acid targeting: Preparation, characterization, and in vitro and in vivo evaluation.

The aim of present study was to develop folic acid (FA)-modified nonionic surfactant vesicles (NISVs, niosomes) as carrier systems for targeted delivery of gambogenic acid (GNA). The FA-GNA-NISVs exhibited a mean particle size of 180.77 ± 2.41 nm with a narrow poly dispersion index of 0.147 ± 0.08 determined by dynamic light scattering. Transmission electron microscopy also revealed that the FA-GNA-NISVs were spherical with double-layer structure. Entrapment efficiency (EE%) and zeta potential of the optimal FA-GNA-NISVs were 87.84 ± 1.06% and -37.33 ± 0.33 mV, respectively. Differential scanning calorimetry demonstrated that the GNA was in a molecular or amorphous state inside the FA-NISVs in vitro release profiles suggested that FA-GNA-NISVs could release GNA at a sustained manner, and less than 60% of GNA was released from the FA-NISVs within 12 hours of dialysis. in vivo pharmacokinetic results illustrated that FA-GNA-NISVs had considerably higher Cmax , area under curve (AUC0 - t ) and accumulation in lung. The cell proliferation study shown that the FA-GNA-NISVs significantly enhanced the in vitro cytotoxicity against A549 cells. Flow cytometry and fluorescence microscopy further demonstrated that the FA-GNA-NISVs increased apoptosis compared with nonmodified GNA-NISVs and free GNA. Moreover, FA-GNA-NISVs induced A549 cell apoptosis in a dose-dependent manner. In addition, cellular uptake assays showed a higher uptake of FA-GNA-NISVs than GNA-NISVs as well as free GNA. Taken together, it could be concluded that FA-GNA-NISVs were proposed as a novel targeting carriers for efficient delivering of GNA to cancers cells.

A novel drug delivery system of mixed micelles based on poly(ethylene glycol)-poly(lactide) and poly(ethylene glycol)-poly(ɛ-caprolactone) for gambogenic acid.

In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and poly(ethylene glycol)-poly(ɛ-caprolactone) (mPEG-PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA-loaded mixed polymeric micelles (GNA-MMs) was prepared by cosolvent evaporation method. The mean average size of GNA-MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA-MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA-MMs were spherical with "core-shell" structures. Compared with free GNA solution, in vitro release of GNA from GNA-MMs showed a two-phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA-MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC50 values on HepG2 cells for GNA-MMs and free GNA were (5.67 ± 0.02) µM and (9.02 ± 0.03) µM, respectively. In addition, GNA-MMs significantly increased the HepG2 cellular apoptosis in a concentration-dependent manner. In conclusion, the results showed that mPEG-PLA/mPEG-PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect.

Differential diagnosis of intestinal tuberculosis from Crohn's disease and primary intestinal lymphoma in China.

BACKGROUND/AIMS: There are many similarities and overlaps in clinical, radiological, endoscopic, and histological features among intestinal tuberculosis (ITB), Crohn's disease (CD), and primary intestinal lymphoma (PIL), and the differential diagnosis of ITB can be very challenging for clinicians. PATIENTS AND METHODS: The clinical, radiologic, endoscopic, and pathological data of 213 patients were analyzed retrospectively. According to the diagnostic criteria and exclusive criteria of ITB, CD, and PIL, 83 patients were recruited and divided into three groups, including 30 cases in the ITB group, 38 cases in the CD group, and 15 cases in the PIL group, and the medical data and statistical analysis were recorded. RESULTS: Rural patients with abdominal pain as the first symptom and with transverse ulcer and caseating granulomas were more common in the ITB group than the CD group, whereas urban patients with stool change as the first symptom, moderate or severe anemia, thickening of intestinal wall, rectal involvement, skipping distribution, prominent lymphoid aggregates, and irregular glands were more common in CD group than ITB group (P < 0.05). Young patients (age < 30 years) with fever, weakness, fatigue, abdominal mass, intestinal perforation, and emergent operation were more common in ITB group than PIL group, whereas thickening of intestinal wall, malignant lymphocytes, limited distribution, and involvement of small intestine occurred more in PIL group than ITB group (P < 0.05). CONCLUSION: The differential diagnosis of ITB from CD and PIL can be made by a combination of clinical manifestation, endoscopy, and pathological examinations.