Efficacy and safety of molnupiravir in patients with Omicron variant vaccine breakthrough COVID-19 infection: a randomized, controlled trial

Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir.Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800 mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up.Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups.Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection.Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796]

Effect of aging on acute pancreatitis through gut microbiota

BackgroundCompared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon.MethodsEighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction.ResultsThe gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not.ConclusionAging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype

Global prevalence of Cryptosporidium spp. in pigs: a systematic review and meta-analysis

Cryptosporidium spp. are significant opportunistic pathogens causing diarrhoea in humans and animals. Pigs are one of the most important potential hosts for Cryptosporidium. We evaluated the prevalence of Cryptosporidium in pigs globally using published information and a random-effects model. In total, 131 datasets from 36 countries were included in the final quantitative analysis. The global prevalence of Cryptosporidium in pigs was 16.3% (8560/64 809; 95% confidence interval [CI] 15.0–17.6%). The highest prevalence of Cryptosporidium in pigs was 40.8% (478/1271) in Africa. Post-weaned pigs had a significantly higher prevalence (25.8%; 2739/11 824) than pre-weaned, fattening and adult pigs. The prevalence of Cryptosporidium was higher in pigs with no diarrhoea (12.2%; 371/3501) than in pigs that had diarrhoea (8.0%; 348/4874). Seven Cryptosporidium species (Cryptosporidium scrofarum, Cryptosporidium suis, Cryptosporidium parvum, Cryptosporidium muris, Cryptosporidium tyzzeri, Cryptosporidium andersoni and Cryptosporidium struthioni) were detected in pigs globally. The proportion of C. scrofarum was 34.3% (1491/4351); the proportion of C. suis was 31.8% (1385/4351) and the proportion of C. parvum was 2.3% (98/4351). The influence of different geographic factors (latitude, longitude, mean yearly temperature, mean yearly relative humidity and mean yearly precipitation) on the infection rate of Cryptosporidium in pigs was also analysed. The results indicate that C. suis is the dominant species in pre-weaned pigs, while C. scrofarum is the dominant species in fattening and adult pigs. The findings highlight the role of pigs as possible potential hosts of zoonotic cryptosporidiosis and the need for additional studies on the prevalence, transmission and control of Cryptosporidium in pigs

Consistency and stability of individualized cortical functional networks parcellation at 3.0 T and 5.0 T MRI

BackgroundIndividualized cortical functional networks parcellation has been reported as highly reproducible at 3.0 T. However, in view of the complexity of cortical networks and the greatly increased sensitivity provided by ultra-high field 5.0 T MRI, the parcellation consistency between different magnetic fields is unclear.PurposeTo explore the consistency and stability of individualized cortical functional networks parcellation at 3.0 T and 5.0 T MRI based on spatial and functional connectivity analysis.Materials and methodsThirty healthy young participants were enrolled. Each subject underwent resting-state fMRI at both 3.0 T and 5.0 T in a random order in less than 48 h. The individualized cortical functional networks was parcellated for each subject using a previously proposed iteration algorithm. Dice coefficient was used to evaluate the spatial consistency of parcellated networks between 3.0 T and 5.0 T. Functional connectivity (FC) consistency was evaluated using the Euclidian distance and Graph-theory metrics.ResultsA functional cortical atlas consisting of 18 networks was individually parcellated at 3.0 T and 5.0 T. The spatial consistency of these networks at 3.0 T and 5.0 T for the same subject was significantly higher than that of inter-individuals. The FC between the 18 networks acquired at 3.0 T and 5.0 T were highly consistent for the same subject. Positive cross-subject correlations in Graph-theory metrics were found between 3.0 T and 5.0 T.ConclusionIndividualized cortical functional networks at 3.0 T and 5.0 T showed consistent and stable parcellation results both spatially and functionally. The 5.0 T MR provides finer functional sub-network characteristics than that of 3.0 T

Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial

Objective: Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial.Methods: A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops.Results: In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) (p = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group (p = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves.Conclusion: Lentinan nasal drops are tolerated well and can shorten the time of virus clearance

Systematic characterization of gene families and functional analysis of PvRAS3 and PvRAS4 involved in rosmarinic acid biosynthesis in Prunella vulgaris

Prunella vulgaris is an important material for Chinese medicines with rosmarinic acid (RA) as its index component. Based on the chromosome-level genome assembly we obtained recently, 51 RA biosynthesis-related genes were identified. Sequence feature, gene expression pattern and phylogenetic relationship analyses showed that 17 of them could be involved in RA biosynthesis. In vitro enzymatic assay showed that PvRAS3 catalyzed the condensation of p-coumaroyl-CoA and caffeoyl-CoA with pHPL and DHPL. Its affinity toward p-coumaroyl-CoA was higher than caffeoyl-CoA. PvRAS4 catalyzed the condensation of p-coumaroyl-CoA with pHPL and DHPL. Its affinity toward p-coumaroyl-CoA was lower than PvRAS3. UPLC and LC-MS/MS analyses showed the existence of RA, 4-coumaroyl-3’,4’-dihydroxyphenyllactic acid, 4-coumaroyl-4’-hydroxyphenyllactic acid and caffeoyl-4’-hydroxyphenyllactic acid in P. vulgaris. Generation and analysis of pvras3 homozygous mutants showed significant decrease of RA, 4-coumaroyl-3’,4’-dihydroxyphenyllactic acid, 4-coumaroyl-4’-hydroxyphenyllactic acid and caffeoyl-4’-hydroxyphenyllactic acid and significant increase of DHPL and pHPL. It suggests that PvRAS3 is the main enzyme catalyzing the condensation of acyl donors and acceptors during RA biosynthesis. The role of PvRAS4 appears minor. The results provide significant information for quality control of P. vulgaris medicinal materials

Reliability and validity of the Chinese post-discharge coping difficulty scale-parent form in parents of premature infants: a multicenter cross-sectional study

BackgroundThe measurement of the coping difficulties of parents of premature infants after discharge provides objective data for nurses to prepare infants for discharge. However, no Chinese scale has been developed to measure parents’ coping difficulties after their premature infants are discharged.AimTo translate the parent version of the Post-Discharge Coping Difficulty Scale (Ped-PDCDS) from English to Chinese and test the reliability and validity of the Chinese version in parents of premature infants.MethodsA multicenter cross-sectional study of 356 parents of premature infants was conducted. The scale was symmetrically translated. Validity was evaluated in terms of content, construct, discriminant, and convergent validities. Reliability was assessed in terms of internal consistency, split-half reliability, and test–retest reliability.ResultsThe Chinese Ped-PDCDS finally contained 11 items. Exploratory and confirmatory factor analyses results showed that the Chinese Ped-PDCDS had three dimensions, and the convergent and discriminant validities of the scale was satisfactory. The overall reliability, split-half reliability, and test–retest reliability of the scale was 0.85, 0.92, and 0.84, respectively.ConclusionThe Chinese Ped-PDCDS has adequate psychometric properties, and is an easy and appropriate instrument for measuring parents’ difficulty in coping with premature infants