Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching.

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.

Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume.

Prunus mume is one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications of Prunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified by in vitro and in vivo studies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.

Anti-inflammatory Activity of Mollugin on DSS-induced Colitis in Mice.

We aimed to explore the anti-inflammatory activity of mollugin extracted from Rubia cordifolia L, a traditional Chinese medicine, on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Thirty C57BL/6 mice were divided into a control group (n=6), a model group (n=6), and three experimental groups (40, 20, 10 mg/kg of mollugin, n=6 each). DSS solution (3%) was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model. Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10. Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3. The changes in colon pathology were detected by hematoxylin and eosin (HE) staining. Interleukin-1ß (IL-1ß) in the serum, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN) in the tissues were measured by enzyme linked immunosorbent assay. Expression levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry. Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model. HE examinations demonstrated that mollugin treatment effectively improved the histological damage (P<0.05). The overproduction of IL-1ß and TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg (P<0.05). Additionally, the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group. Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

Anti-diarrheal and anti-inflammatory activities of aqueous extract of the aerial part of Rubia cordifolia.

BACKGROUND: In Shaanxi province, China, the aqueous extract of Rubia cordifolia's aerial part (AERCAP) is traditionally used to manage diarrhea. However, there is no scientific evidence to verify the safety and efficacy of its use. The aim of this study was to investigate the anti-diarrheal and anti-inflammatory effects of AERCAP by using a rodent model. METHODS: The anti-diarrheal effects were studied by senna leaf-induced diarrheal and intestinal transit experiments in mice. The anti-inflammatory activity was investigated by trinitrobenzenesulfonic acid (TNBS)-induced colonic inflammation in rats. RESULTS: The results indicated that AERCAP delayed the onset of semi-solid feces, reduced the evacuation index (EI) in senna leaf-induced diarrheal in mice, and inhibited the propulsive movement in castor oil-induced intestinal transit but not in the normal intestinal transit test. The results were compared with the standard anti-diarrheal drug loperamide. Additionally, oral treatment with AERCAP significantly decreased the macroscopic damage area, improved the microscopic structure, and reduced the malondialdehyde (MDA) content, IL-1ß and TNF-α levels in colonic tissue compared with the TNBS control group in rats. CONCLUSIONS: AERCAP exhibited anti-diarrheal and anti-inflammatory activities in a rodent model. The study validated the traditional use of the plant in Chinese herbal medicine as a valuable natural remedy for the treatment of diarrhea.

[A new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique: a case report].

OBJECTIVE: To design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique and explore a method to solve the necroses of allocartilage in hemi joint allotransplantation. METHODS: Design the new custom-made artificial articular cartilage of femoral condyle. The allograft and the patient distal femurs were scanned with Picker 6000 spiral computed tomography (CT) with 1.0 slice thickness and pitch of 1.5, reconstructed the distal femurs in Voxel Q image workstation with volume rendering technique. Then downloaded the transaxial 2D image data to personal computer at 0.1 mm interval and converted it into 2D digitized contour data by using image processing software developed by our team. The 3D wire frame and solid images of femoral condyle could be reconstructed when the 2D digitized contour data were input into image processing software Surfacer 9.0 (Imageware Company, USA). Subsequently based on the clinical experience and the need of design, the 3D contour image of articular cartilage was extracted from the surrounding. Based on the extracted 3D contour image, the computer-aided design (CAD) of the custom-made artificial articular cartilage was accomplished in Surfacer software, converted the CAD model into RP data format. Standard triangularization language, imported into the LPS600 rapid prototyping machine (Hengtong Company, Xi'an Jiaotong University, China), and the resin prototype was achieved. Then the resin model was used as a positive mould to build up a silica gel negative mould, the negative mould was sent to the factory to manufacture Ti-6Al-4V alloy articular cartilage through ordinary mould-melted founding process. Finally, the whole metal cartilage was completed after melting two special cages on it. A patient was selected to clinical applying. RESULTS: A new custom-made artificial articular cartilage of femoral condyle was made. It was press-fit well to the subchondral bone of the allograft bone. The patient's one and half year follow-up result was excellent. CONCLUSIONS: We design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique. The result shows that the manufacturing process has the advantage of rapidness and precision that are very important for individualized artificial implant manufacturing. The artificial articular cartilage is press-fit well and could be a good idea to solve the necroses of allocartilage in hemijoint allotransplantation.