Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Comprehensive analysis of the clinical significance, immune infiltration, and biological role of MARCH ligases in HCC.

The membrane-associated RING-CH (MARCH) family, a member of the E3 ubiquitin ligases, has been confirmed by a growing number of studies to be associated with immune function and has been highlighted as a potential immunotherapy target. In our research, hepatocellular carcinoma (HCC) patients were divided into C1 and C2 MARCH ligase-related patterns by the non-negative matrix factorization (NMF) algorithm. Multiple analyses revealed that the MARCH ligase-related cluster was related to prognosis, clinicopathological characteristics, and the tumor immune microenvironment (TIME). Next, the signature (risk score) of the MARCH prognosis was constructed, including eight genes associated with the MARCH ligase (CYP2C9, G6PD, SLC1A5, SPP1, ANXA10, CDC20, PON1, and FTCD). The risk score showed accuracy and stability. We found that the correlations between risk score and TIME, tumor mutation burden (TMB), prognosis, and clinicopathological characteristics were significant. Additionally, the risk score also had important guiding significance for HCC treatment, including chemotherapy, immunotherapy, and transarterial chemoembolization (TACE).

[Sensitivity Comparison Experiment of Four Testing Methods for Helicobacter pylori].

Objective: To measure with standard microbiology methods the sensitivity of 4 commonly used testing methods for Helicobacter pylori (Hp) and to conduct a comparative study of the correlations and differences across the 4 methods. Methods: With the Hp standard strain (SS1) as the reference, colony forming units (CFU) as the units of quantitative analysis for detection performance, and gradient dilution of SS1 suspension as the simulation sample, we measured the sensitivity of 4 Hp testing methods, including bacterial culture, rapid urease test, antigen test, and quantitative fluorescent PCR. CFU values at different concentrations corresponding to the 4 commonly used Hp testing methods were documented and the correlations and differences were analyzed accordingly. Results: The sensitivity of Hp bacterial culture, rapid urease test, antigen test and quantitative fluorescent PCR was 2.0×10 CFU/mL, 2.0×10 5 CFU/mL, 2.0×10 5 CFU/mL, and 2.0×10 2 CFU/mL, respectively. Conclusion: The testing turnover time and sensitivity of different laboratory methods for Hp testing varied significantly. The quantitative fluorescent PCR and bacterial culture both showed relatively high sensitivity, but bacterial culture has complicated operation procedures and is too time-consuming. The rapid urease test and antigen test both were simple and quick to perform, but showed low sensitivity. For clinical and laboratory testing of Hp, appropriate testing method that can identify the corresponding changes of Hp should be selected according to the actual testing purpose.

Down-regulation of circPTTG1IP induces hepatocellular carcinoma development via miR-16-5p/RNF125/JAK1 axis.

Circular RNAs are known to regulate the biological processes of hepatocellular carcinoma (HCC), and humans with Down syndrome are at low risk of developing solid tumors due to the amplification of several tumor suppressor genes on human chromosome 21 (HSA21). Here, we aimed to investigate the potential role of circRNAs originating from HSA21 in the progression of HCC. CircRNA-sequencing was performed to analyze differentially expressed circRNAs in 4 HCC and peritumor tissues, and circRNAs originating from HSA21 were further analyzed. Circ_0061984 (circPTTG1IP) was chosen for further study because it showed the lowest expression in HCC tissues, and qRT-PCR was used to confirm the expression of circPTTG1IP in HCC patient tissues. The biological function of circPTTG1IP was detected in HCC cells both in vivo and in vitro. Moreover, luciferase reporter assays, circRNA immunoprecipitation, and fluorescence in situ hybridization (FISH) were used to investigate the potential mechanism of circPTTG1IP. Finally, the possible mechanisms of filgotinib in circPTTG1IP-driven HCC were assessed. CircPTTG1IP expression was decreased in HCC compared to peritumoral tissues. Moreover, low circPTTG1IP expression was revealed to be associated with a poor prognosis of HCC patients. Elevation of circPTTG1IP was revealed to inhibit HCC development both in vitro and in vivo. Mechanistically, circPTTG1IP was shown to function as a competing endogenous RNA (ceRNA) of RNF125 by binding miR-16-5p to increase the level of the E3 ubiquitin ligase RNF125, which further ubiquitinated and degraded JAK1 protein. Finally, we demonstrated that administration of filgotinib, a JAK1 inhibitor, restricted HCC progression induced by low circPTTG1IP expression. Thus, we revealed that circPTTG1IP is a novel tumor suppresser circRNA in HCC and that a low circPTTG1IP level promotes HCC development via the miR-16-5p/RNF125/JAK1 axis. Patients with low circPTTG1IP may benefit from filgotinib treatment.

[Preparation and Release Properties of Helicobacter pylori Recombinant Protein PLGA Microspheres and PLGA-Chitosan Microspheres].

OBJECTIVE: To preparethe poly lactic-co-glycolic acid (PLGA) microspheres and PLGA-chitosan microspheres containing Helicobacter pylori recombinant protein, namely the BIB protein, and to explore their optimal preparation parameters and in vitro release performance in gastric and intestinal fluids. METHODS: Double emulsions (water-in-oil-in-water, or W1/O/W2) solvent evaporation method was used to prepare the BIB-PLGA microspheres and the BIB-PLGA-chitosan microspheres. Univariate analysis was done to study the impact of the water-to-oil ratio (W1/O), PLGA mass fraction and PVA concentration on the morphology, particle size, polydispersity index (PDI), encapsulation efficiency (EE), and drug loading (DL) so as to identify the optimal parameters. Bicinchoninic acid (BCA) assay was used to determine the protein concentration and the release efficiency of BIB. RESULTS: The optimal preparation parameters identified in the study were as follows: W1/O at 1∶2, PLGA mass fraction at 5%, and PVA mass fraction at 0.2%. The BIB-PLGA microspheres were found to be (2.11±0.08) µm in particle size, 0.35±0.18 in PDI, (78.20±1.73)% in EE and (10.58±0.23)% in DL. The BIB-PLGA-chitosan microspheres were (2.28±0.52) µm in particle size, 0.39±0.54 in PDI, and (78.87±1.30)% and (15.50±0.25)% in EE and DL, respectively. Both BIB-PLGA microspheres and BIB-PLGA-chitosan microspheres showed slow-release property in gastric and intestinal fluids in vitro, with BIB-PLGA-chitosan microspheres showing better slow-release performance. CONCLUSION: The BIB-PLGA microspheres and BIB-PLGA-chitosan microspheres prepared with the double emulsions solvent evaporation method showed high DL and EE, controllable particle sizes, dispersive appearance, and slow-release property in gastric and intestinal fluids in vitro.

New insights for the risk of bisphenol A: inhibition of UDP-glucuronosyltransferases (UGTs).

Bisphenol A (BPA), the important endocrine-disrupting chemical (EDC), has been reported to be able to induce various toxicity. The present study aims to understand the toxicity behavior of bisphenol A through evaluating the inhibition profile of bisphenol A towards UDP-glucuronosyltransferase (UGT) isoforms. In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as probe reaction for all the tested UGT isoforms. The results showed that bisphenol A exerted stronger inhibition towards UGT2B isoforms than UGT1A isoforms. Furthermore, the inhibition kinetic type and parameters (K(i)) were determined for the inhibition of bisphenol A towards UGT2B4, 2B7, 2B15, and 2B17. Bisphenol A exhibited the competitive inhibition towards UGT2B4, and noncompetitive inhibition towards UGT2B7, 2B15 and 2B17. The inhibition kinetic parameters (K(i)) were calculated to be 1.1, 32.6, 5.6, and 19.9 µM for UGT2B4, 2B7, 2B15 and 2B17, respectively. In combination with the in vivo concentration of bisphenol A, the elevation of exposure dose was predicted to increase by 29.1%, 1%, 5.7%, and 1.6% for UGT2B4, 2B7, 2B15, and 2B17, indicating the high influence of bisphenol A towards the in vivo UGT2B isofroms-mediated metabolism of xenobiotics and endogenous substances. All these data provide the supporting information for deeper understanding of toxicology of bisphenol A.