Comparative efficacy of Chinese patent medicines in patients with carotid atherosclerotic plaque: a Bayesian network meta- analysis.

BACKGROUND: Traditional Chinese patent medicines (TCPMs) have been widely used to treat carotid atherosclerotic plaque (CAP) in China. However, systematic evaluation of the clinical efficacy of TCPMs for CAP is still unknown, and the comparative efficacy of different TCPMs is unclear. OBJECTIVES: This study aims to compare and rank the effectiveness and safety of different TCPMs in treating CAP using a Bayesian network meta- analysis (NMA). METHODS: This NMA was performed according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) Extension Statement. Eight databases were searched from their inception to August 2023 for randomized controlled trials (RCTs). The articles regarding eligibility and extracted data were screened independently by two authors. The Cochrane Risk of Bias tool was used to evaluate quality and bias. The change of carotid artery intimal- medial thickness (IMT), carotid maximal plaque area, carotid atherosclerotic plaque Course score, serum lipid levels, CRP, and adverse events rate (AER) were used as outcomes. Data from each RCTs were first pooled using random- effect pairwise meta- analyses and illustrated as odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence interval (CI). NMAs were performed using Stata17.0 software and the GeMTC package of R software to evaluate the comparative effectiveness of TCPMs, and displayed as ORs or SMDs with 95% CI. A Bayesian hierarchical random- effects model was used to conduct NMAs using the Markov Chain Monte Carlo algorithm. The GRADE partially contextualised framework was applied for NMA result interpretation. RESULTS: NMA included 27 RCT trials with 4131 patients and nine types of TCPMs. Pairwise meta- analyses indicated that Conventional Western medicine (CWM) + TCPM was superior to CWM in reducing the IMT (SMD: - 1.26; 95% CI - 1.59 to - 0.93), the carotid maximal plaque area (SMD - 1.27; 95% CI - 1.71, - 0.82) and the carotid atherosclerotic plaque Course score (SMD - 0.72; 95% CI 95% CI - 1.20, - 0.25). NMAs demonstrated that CWM + Jiangzhiling pill (JZL) with SUCRA 70.6% exhibited the highest effective intervention for reducing IMT. CWM + SXBX (Shexiang baoxin pill) was superior to other TCPMs in reducing the carotid maximal plaque area (83.0%), the atherosclerotic plaque Course score (92.5%), TC (95.6%) and LDL (92.6%) levels. CWM + NXT (Naoxintong capsule), CWM + XS (Xiaoshuang granules/enteric capsule), and CWM + ZBT (Zhibitai) were superior to other CPMs in improving TG (90.1%), HDL (86.1%), and CRP (92.6%), respectively. No serious adverse events were reported. CONCLUSIONS: For CAP patients, CWM + XSBX was among the most effective in reducing carotid maximal plaque area, atherosclerotic plaque Course score, TC and LDL levels, and CWM + JZL was the most effective in reducing IMT. Overall, CWM + XSBX may be considered an effective intervention for the treatment of CAP. This study provides reference and evidence for the clinical optimization of TCPM selection in CAP treatment. More adequately powered, well- designed clinical trials to increase the quality of the available evidence are still needed in the future due to several limitations.

Traditional Chinese Medicine for the Common Cold: Evidence and Potential Mechanisms.

Traditional Chinese medicine (TCM) has a history of over 2000 years in treating infectious diseases, among which the clinical treatment of the common cold (colds) and influenza (flu) is the most widespread and well-established. It is difficult to tell the difference between a cold and the flu based on the symptoms alone. The flu vaccine protects against influenza, but there is no vaccine or specific medication to protect against the common cold. Due to the lack of a reliable scientific basis, TCM has not received sufficient attention in Western medicine. Therefore, we systematically evaluated the scientific evidence proving the efficacy of TCM intervention in treating colds for the first time by examining theoretical principles, clinical research, and pharmacological perspectives, as well as the mechanisms behind this efficacy. In TCM theory, there are four important external environmental factors that may cause a cold, which are called "cold, heat, dryness, and dampness". The scientific basis for this theory has been described and will help researchers to understand and recognize its importance. The results of the systematic review of high-quality randomized controlled clinical trials (RCTs) have shown that TCM is effective and safe for the treatment of colds. Therefore, TCM might be used as a complementary or alternative approach to cold treatment and management. Some clinical trials have demonstrated that TCM may have potential therapeutic effects in preventing colds and treating their sequelae. However, more high-quality, large-scale randomized controlled trials should be conducted in the future for further verification. Pharmacological studies have shown that active ingredients extracted from TCM for treating colds have antiviral, anti-inflammatory, immune-regulating, and anti-oxidative properties. We expect that this review will guide the optimization and rationalization of TCM clinical practice and scientific research in the treatment of colds.

Berberine, a potential prebiotic to indirectly promote Akkermansia growth through stimulating gut mucin secretion.

BACKGROUND: Akkermansia spp. plays important roles in maintenance of host health. Increasing evidence reveals that berberine (BBR) may exert its pharmacological effects via, at least partially, promotion of Akkermansia spp. However, how BBR stimulates Akkermansia remains largely unknown. PURPOSE: In this study, we investigated the mechanism underlying the Akkermansia-promoting effect of BBR. MATERIALS AND METHODS: The effect of BBR on Akkermansia was assessed in BBR-gavaged mice and direct incubation. The influence of BBR on intestinal mucin production was determined by alcian-blue staining and real-time PCR. The feces were analysis by gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) metabolomics. The role of polyamines in BBR-elicited mucin secretion and Akkermansia growth was evaluated by administration of difluoromethylornithine (DFMO) in mice. RESULTS: Gavage of BBR dose-dependently and time-dependently increased the abundance of Akkermansia in mice. However, it did not stimulate Akkermansia growth in direct incubation, suggesting that BBR may promote Akkermansia in a host-dependent way. Oral administration of BBR significantly increased the transcription of mucin-producing genes and mucin secretion in colon. Untargeted metabolomics analysis showed that BBR increased polyamines production in feces which are known to stimulate goblet cell proliferation and differentiation, but treatment with eukaryotic polyamine synthase inhibitor DFMO did not abolish the stimulating effect of BBR on mucin secretion and Akkermansia growth, indicating that the gut bacteria-derived but not the host-derived polyamines may involve in the BBR-promoted Akkermansia growth. CONCLUSIONS: Our results reveal that BBR is a promising prebiotic for Akkermansia, and it promotes Akkermansia growth via stimulating mucin secretion in colon.

[Effect of rapid decompression on rat multifocal electroretinogram].

OBJECTIVE: To observe the effect of rapid decompression on rat multifocal electroretinogram (mfERG) and to explore the characteristics of the retinal function impairment due to decompression sickness at early stage. METHODS: Twenty rats were randomly divided into 4 groups: normal control (NC) group, safe decompression (SD) group, 0 h and 6 h after rapid decompression (RD0 and RD6) groups. The treated rats in safe decompression group and each rapid decompression group were exposed in hyperbaric cabin and air pressure in the cabin rose up to 1.0 MPa in 30 s and lasted for 5.5 min. The pressure decreased to normal pressure in 55 s as for the treatment of rapid compression while air pressure of safe decompression decreased to normal pressure according to an animal safe decompression protocol. The mfERG parameters of one eye each rat were recorded by RETIscan 3.15 system. RESULTS: Rapid decompression increased noise, delayed latent period and reduced amplitude in mfERG. The topographic map showed that the P1 wave response density in RD0 group was lower than that in NC and SD groups and higher than that in RD6 group in peripheral regions. The amplitudes of sum response density in NC, SD, RD0 and RD6 groups were (71.1 ± 7.5), (53.6 ± 9.3), (38.2 ± 13.1) and (18.4 ± 7.7) µV, respectively, and there was statistical difference among them (F = 17.313, P < 0.01). The P1 wave response densities of RD0 and RD6 groups were lower than that of NC group in 4 quadrants (P < 0.05) and the P1 wave amplitudes of RD0 and RD6 groups decreased in supranasal and supratemporal quadrants (P < 0.05). The P1 wave amplitudes of RD0 and RD6 groups were less than these of NC and SD groups in supranasal and supratemporal quadrants (P < 0.05). In 5 rings, the response densities of RD0 and RD6 groups were lower than these of NC and SD groups (P < 0.05) and the P1 and N1 wave amplitudes were less than these of NC and SD groups (P < 0.05). The P1 and N1 wave amplitudes of RD6 group were lower than those of RD0 group (P < 0.05). CONCLUSION: Rapid decompression can cause characteristic changes of mfERG and the major involved parts are superior retina and juxtaprepapillary region.

Effects of anti-VEGF agents on rat retinal Müller glial cells.

PURPOSE: To evaluate the effects of an anti-rat vascular endothelial growth factor antibody (ARVA) and bevacizumab (Avastin) on rat retinal Müller glial cells (RMGCs) in vivo and in vitro. METHODS: Rat RMGCs were identified and cultivated, and were then treated with bevacizumab (0.1, 0.25, and 1 mg/ml), ARVA (0.1, 0.5, and 1 microg/ml), or 1 mg/ml of rat immunoglobulin G (IgG) for 12, 24, 48, and 72 h. The numbers of viable RMGCs were determined using a trypan blue dye exclusion assay and a methyl thiazolyl tetrazolium colorimetric assay. In the in vivo study, the rats received intravitreal injections of 5 microl bevacizumab (3.75 mg/ml), ARVA (15 microg/ml), and rat IgG (1 mg/ml). The electroretinogram was recorded. Seven days after the injections, histopathologic changes and glial fibrillary acidic protein expression of RMGCs in the retina were analyzed by immunohistochemistry with hematoxylin-eosin and fluorescent staining. RESULTS: After exposure to bevacizumab at various concentrations for various periods of time, the stained cell numbers and optical density values of mitochondrial dehydrogenase activity of RMGCs had no significant differences (p>0.05) from those of the control group and IgG medium. In the stained cells, ARVA demonstrated a dose-dependent increase. Compared with those treated for 12 and 24 h, the increase of stained cells treated with 0.5 and 1 microg/ml ARVA at 48 and 72 h was very significant (p<0.01). The optical densities of RMGCs exposed to 0.5 and 1 microg/ml of ARVA at 48 and 72 h were significantly lower than cells exposed to a fresh culture medium (p<0.01). The histology of both treated and control eyes after intravitreal injection was similar and showed no anatomic signs of toxicity. There were no obvious glial fibrillary acidic protein upregulations of RMGCs in all groups. The scotopic electroretinogram responses to flashes of light in the control and treated eyes had similar b-wave amplitudes. CONCLUSIONS: Intravitreal bevacizumab and ARVA had no short-term, direct retinal toxicity in rats. Bevacizumab exerts no inhibition on rat RMGCs, while ARVA at higher doses (over 0.5 microg/ml) may be harmful to the growth of RMGCs.