Integrated widely targeted metabolomics and network pharmacology revealed quality disparities between Guizhou and conventional producing areas of Codonopsis Radix.

Introduction: With the internationalization of traditional Chinese medicine, the demand for medicinal and edible Codonopsis Radix (CR) has increased, and its medicinal resources have attracted attention. CR is a well-known traditional Chinese medicine with a long pharmaceutical and edible history. The Guizhou province in China has abundant CR resources, but in the absence of systematic studies on species identification and chemical compositions, the capacity of the capacity of the province to CR resource has not been fully utilized. Methodology: We used plant morphology and DNA barcoding techniques to identify Luodang (LD) and Weidang (WD) species. To investigate the differences in metabolites between LD and WD, as well as three Chinese Pharmacopeia CRs, and to predict pharmacological mechanisms of action for the dominant differential metabolites, we utilized widely targeted metabolomics and network pharmacology. The results also revealed the material basis for the excellent food properties of both LD and WD. Results: The plant traits and DNA barcoding molecular identification results indicated that Luodang and Weidang from Guizhou were Codonopsis tangshen and Codonopsis pilosula, respectively. Widely targeted metabolomics analysis revealed that a total of 1,116 metabolites from 14 categories, including phenolic acids, lipids, flavonoids, were found in five CRs and shared 1,054 (94.4%) metabolites. LD and WD each contained 3 and 10 dominant differential metabolites, respectively, which were primarily flavonoids and amino acids. Amino acids, phenolic acids, and organic acids play important roles in their excellent food attributes. In CR, eight dominant differential metabolites were discovered for the first time, including isoorientin-7-O-(6″-feruloyl) glucoside, N-formyl-L-methionine, and cyclo (Phe-Glu), among others. Network pharmacology analyses showed that, in LD, dominant differential metabolites were closely related to anti-tumor, cardiovascular disease improvement, nervous system protection, and metabolic disease treatment, whereas in WD, they were closely related to nervous system protection and cardiovascular disease improvement. Conclusion: The species of LD and WD were included in the Chinese Pharmacopeia, and their metabolite profiles were remarkably similar to CR from traditional producing areas. Therefore, LD and WD can be used and promoted medicinally as CR, and they have potential value for new drug development. This study enriched the database of CR compounds and provided a reference for quality control, resource development, and new drug development of CR.

Systematic review with meta-analysis: loss of response and requirement of ustekinumab dose escalation in inflammatory bowel diseases.

BACKGROUND: Ustekinumab is effective in treating Crohn's disease (CD) and ulcerative colitis (UC). However, the loss of response (LOR) to ustekinumab and the efficacy of dose escalation have not been systematically explored. METHODS: Databases were searched for eligible studies from inception through July 2021. Summary estimates were pooled, and subgroup analyses were performed to explore heterogeneity. RESULTS: We included 14 studies (CD: 13; UC: 1). In CD patients, the annual risk of LOR to ustekinumab and dose escalation among primary responders was 21% (95% confidence interval [CI] 12-31%, 1530 person-years, n = 9) per person-year and 25% (95% CI 12-32%, 657 person-years, n = 5) per person-year respectively. Clinical response was regained in 58% (95% CI 49-67%, 279 patients, n = 8) of secondary non-responders after dose escalation (interval reduction or intravenous reinduction). In UC patients, no studies provided data on LOR, but only one study showed that 35% (100/284) of patients underwent dose escalation (or sham dose adjustment), leading to an annual risk of dose escalation of 18% per person-year. After dose escalation, 58% (14/24) of the patients regained symptomatic remission. CONCLUSIONS: Primary responders with CD experienced LOR to ustekinumab at a risk of 21% per person-year and required dose escalation at a risk of 25% per person-year. Fifty-eight per cent of secondary non-responders with CD may benefit from dose escalation. LOR has not been well characterized in patients with UC.

Biocompatibility and retinal support of a foldable capsular vitreous body injected with saline or silicone oil implanted in rabbit eyes.

INTRODUCTION: The aim of this study was to evaluate over a 180-day period the biocompatibility and retinal support of a foldable capsular vitreous body injected with either saline or silicone oil implanted in rabbit eyes. METHODS: A standard three-port pars plana vitrectomy was performed, and foldable capsular vitreous bodies were implanted into the vitreous cavity of rabbit eyes (n = 18). Silicone oil tamponade was used as the control group (n = 5). Of the foldable capsular vitreous body-implanted eyes, either saline (n = 9) or silicone oil (n = 9) was injected into the foldable capsular vitreous body to support the retina. The treated eyes were examined using a slit lamp with a non-contact slit-lamp lens, a tonopen, a non-contact specular microscope and a B-scan ultrasound during the 180-day implantation period. A histological examination was performed at 90 and 180 days. RESULTS: During the 180-day implantation period, no significant corneal keratopathy or intraocular inflammation was noted, and the intraocular pressure (IOP) and corneal endothelial numbers remained steady among the three groups. B-scan ultrasonography showed a smoothly increased echogenicity in front of the retina in group of foldable capsular vitreous bodies injected with saline. Gross examination showed that the foldable capsular vitreous bodies injected with saline or silicone oil smoothly supported the retina. The saline or silicone oil inside the foldable capsular vitreous body was homogeneous, transparent and filled the foldable capsular vitreous body. Histological examination showed no obvious abnormality of the cornea, ciliary body or retina in the foldable capsular vitreous body-implanted eyes. CONCLUSIONS: These results suggest that foldable capsular vitreous bodies injected with either saline or silicone oil showed good biocompatibility and retinal support in rabbit eyes over a 180-day implantation time.

[Experimental study of PVPP/silicone composite automatic expanded material as implants].

OBJECTIVE: To study the feasibility of Polyvinylpolypyrrolidone (PVPP)/silicone composite automatic expanded material as implants. METHODS: The PVPP hydrogel was mixed with silicone through the location at the high temperature. Implants with different ratio of PVPP to silicone were placed under the back and nose skin in 24 New Zealand rabbits. The surrounding tissue reaction, material and skin expansion were observed and compared with those with pure silicone implants. RESULTS: The study lasted for 200 days. Compared with pure silicone implants, the composite material could expand automatically and stop expanding at about 2 weeks after implantation. Histological study showed similar inflectional and foreign body reaction around the composite material and the pure silicone. CONCLUSIONS: Compared with pure silicone, the PVPP/silicone composite implant has the advantage of automatic expansion, so as to expand the soft tissue.