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 .

Au-Ag OHCs-based SERS sensor coupled with deep learning CNN algorithm to quantify thiram and pymetrozine in tea.

Pesticide residue detection in food has become increasingly important. Herein, surface-enhanced Raman scattering (SERS) coupled with an intelligent algorithm was developed for the rapid and sensitive detection of pesticide residues in tea. By employing octahedral Cu2O templates, Au-Ag octahedral hollow cages (Au-Ag OHCs) were developed, which improved the surface plasma effect via rough edges and hollow inner structure, amplifying the Raman signals of pesticide molecules. Afterward, convolutional neural network (CNN), partial least squares (PLS), and extreme learning machine (ELM) algorithms were applied for the quantitative prediction of thiram and pymetrozine. CNN algorithms performed optimally for thiram and pymetrozine, with correlation values of 0.995 and 0.977 and detection limits (LOD) of 0.286 and 29 ppb, respectively. Accordingly, no significant difference (P greater than 0.05) was observed between the developed approach and HPLC in detecting tea samples. Hence, the proposed Au-Ag OHCs-based SERS technique could be utilized for quantifying thiram and pymetrozine in tea.

Whole-course nutritional support therapy and indicators in head and neck cancer surgery.

BACKGROUND AND OBJECTIVES: This study investigated the effect of continuous perioperative nutritional support provided by a multidisciplinary team (MDT) to patients who underwent surgery for head and neck cancer (HNC). METHODS AND STUDY DESIGN: This study enrolled 99 patients with HNC and divided them into two groups: a management group (n=48), comprising patients who underwent surgery between August and December 2020 and received continuous perioperative nutritional support from the MDT; and a control group (n=51), comprising patients who underwent surgery between June and December 2017 and received routine nutritional guidance. Data on weight, nutritional indicators, and the prognostic nutritional index (PNI) were collected. We compared the changes in weight, nutritional indicators, PNI, Patient-Generated Subjective Global Assessment (PG-SGA) scores, and body composition. Factors influencing the PNI were analysed. RESULTS: The minimum weight, nutritional indicator, and PNI values observed postoperatively and at discharge were lower than those observed at admission. The serum nutritional index values observed at discharge and minimum PNI values observed postoperatively and at discharge were higher in the management group than in the control group. The PG-SGA score at 2 weeks postoperatively was higher than that on the day of surgery in the management group. The discharge PNI was influenced by management and age in these HNC surgical patients. In the management group, body composition data did not differ significantly between the preoperative and 1-, 2-, and 3-week postoperative time points. CONCLUSIONS: Continuous perioperative nutritional support by an MDT can improve the weight and serum nutritional index of patients receiving surgery for HNC and improve the PNI at discharge.

Co-occurrence of antimicrobial and metal resistance genes in pig feces and agricultural fields fertilized with slurry.

Antimicrobial resistance constitutes a global challenge to public health. The common addition of Zn, Cu and other metals to animal feed and the widespread presence of metal ions in livestock and their receiving environments may be a factor that facilitates the proliferation of antimicrobial resistance via co-selection of antimicrobial resistance genes (ARGs) and metal resistance genes (MRGs). However, the extent of co-selection is not yet fully understood. In this study, we used a metagenomic approach to profile ARGs, MRGs and mobile genetic elements (MGEs) known to constitute potential ARG and MRG vectors of transmission, and we determined the concentration of metal ions to assess the interrelationships between the occurrence of ARGs, MRGs and metal concentrations in samples from pig farms in China. Samples analyzed included fresh pig feces, soils fertilized with treated slurry, and sediments from aquatic environments, where effluent from treated slurry was discharged. Resistance genes to tetracycline and zinc were the most commonly observed ARGs and MRGs for all three types of samples. Significant correlations were observed between the abundance of ARGs and MRGs, and between ARGs/MRGs and MGEs, and between metal and ARGs/MGEs as documented by Pearson's correlation analysis (r > 0.9, P < 0.001). Further network analysis revealed significant co-occurrence between specific ARGs and MRGs, between ARGs/MRGs and MGEs, and between specific metals (Zn, Cr, and Mn) and ARGs and MGEs. Collectively, our findings demonstrate a high level of co-occurrence of antimicrobial and metal resistance genes in slurry from pig farms and their surrounding environments. The results suggest that metals added to pig feed might facilitate co-selection of ARGs and MGEs in the pig production environments, thereby resulting in a bigger pool of mobile ARGs.

Improving the discomfort and satisfaction of colonoscopy by distraction with smartphones: A prospective randomized controlled study.

BACKGROUND: Colonoscopy is an uncomfortable procedure. Distraction is thought to reduce pain by decreasing the amount of attention a person spends on a painful stimulus. We aimed to assess the usefulness of smartphones on discomfort associated with the colonoscopy. METHODS: We designated 360 enrolled patients according to prospective randomized controlled study into two groups, including smartphone (SP) group (Relaxation by smartphones) and Control group (No relaxation). Measured outcomes included the discomfort, satisfaction, polyp detection rate and the willingness to repeat colonoscopy were analyzed between groups. RESULTS: The pain and distension scores of SP group patients were significantly lower than those of the Control group (2.18 ±â€Š2.80 vs 3.55 ±â€Š3.07, P < .001; 4.15 ±â€Š2.35 vs 4.79 ±â€Š2.36, P = .011, respectively). Importantly, patient-reported satisfaction scores of the SP group were significantly higher than those of the Control group (96.45 ±â€Š7.17 vs 91.12 ±â€Š10.49, respectively; P < .001). Moreover, although there were no statistical differences, patients using smartphones were more likely to have shorter reach cecum times (09m:11 s vs 07m:37 s, P = .116) and more polyp detection rate (13.3% vs 9.4%, P = .246). In addition, more patients using smartphones were willing to repeat colonoscopy but no statistical difference (85.0% vs 81.7%, P = .396). CONCLUSION: Patient using smartphone is a special manner to increase satisfaction during colonoscopy with a less discomfort and is more likely to be polyp detection rate.

Antihypertensive Activity of Eucommia Ulmoides Oliv: Male Flower Extract in Spontaneously Hypertensive Rats.

Eucommia ulmoides Oliv. is a traditional medical plant in Asia; however, it is still unknown whether Eucommia male flowers have an antihypertensive activity. In this study, we found that the aqueous extract of Eucommia ulmoides Oliv. male flowers can lower the blood pressure of SHR in a dose-dependent manner. Mechanistic studies suggested that the aqueous extract of male flowers can promote the mRNA and protein expressions of ACE2 in the kidney of SHR. ELISA assay showed that the plasma levels of ANG II was decreased, while ANG-(1-7) was increased in SHR treated with the aqueous extract of male flowers. ACE2 inhibitor DX600 can reverse the aqueous extract of Eucommia ulmoides Oliv. male flower-induced downregulation of Ang II and upregulation of Ang-(1-7), as well as the reduction of blood pressure in SHR. Moreover, Ang-(1-7)-Mas receptor antagonist A-779 abolished the antihypertensive effects of the aqueous extract of Eucommia ulmoides Oliv. male flower in SHR. The aqueous extract of Eucommia ulmoides Oliv. male flowers exhibited an antihypertensive action through the activation of ACE2-Ang-(1-7)-Mas signaling pathways in spontaneously hypertensive rats.

[Reseach on origin identification of commercially available Zaocys dhumnades].

Through market investigation, the adulteration of Zaocys dhumnades on markets was found out, and samples of authentic and adulterated Z. dhumnades on markets were collected. The origin and properties of the adulterated Z. dhumnades were studied in order to provide reference for the identification of Z. dhumnades. The counterfeit Z. dhumnades sold on markets were as follows: Ptyas korros, P. mucosus, Najanaja atra, Sinonatrix annularis, Dinodon septentrionalis, etc. It is found that there existed a obvious difference between the traits of the Z. dhumnades and counterfeits. Genuine Z. dhumnades with "sword ridge" "iron tail", strongly ribbed scales and other features, is the key point to identify the difference from adulterants.

Influence Factors of the Pharmacokinetics of Herbal Resourced Compounds in Clinical Practice.

Herbal medicines have been used to prevent and cure diseases in eastern countries for thousands of years. In recent decades, these phytotherapies are becoming more and more popular in the West. As being nature-derived is the essential attribute of herbal medicines, people believe that taking them for diseases treatment is safe enough and has no side-effects. However, the efficacy of herbal resourced compounds (HRC) depends on the multiple constituents absorbed in the body and their pharmacokinetics. Thus, many factors will influence the clinical practice of HRC, i.e., their absorption, distribution, metabolism, and excretion (ADME). Among these factors, herb-drug interaction has been widely discussed, as these compounds may share the same drug-metabolizing enzymes and drug transporters. Meanwhile there are many other potential factors that can also change the ADME of HRC, including herb pretreatment, herb-herb interactions, pathological status, gender, age of patient, and chemical and physical modification of certain ingredients. With the aim of ensuring the efficacy of HRC and minimizing their clinical risks, this review provides and discusses the influence factors and artificial improvement of the pharmacokinetics of HRC.

Na+/H+ Exchanger Regulates Amino Acid-Mediated Autophagy in Intestinal Epithelial Cells.

BACKGROUND/AIMS: Dysfunctional autophagy has been reported to be associated with aberrant intestinal metabolism. Amino acids can regulate autophagic activity in intestinal epithelial cells (IECs). Na+/H+-exchanger 3 (NHE3) has been found to participate in the absorption of amino acids in the intestine, but whether NHE3 is involved in the regulation of autophagy in IECs is unclear. METHODS: In the present study, an amino acid starvation-induced autophagic model was established. Then, the effects of alanine and proline with or without the NHE inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) were evaluated. Autophagy was examined based on the microtubule-associated light chain 3 (LC3) levels, transmission electron microscopy (TEM), tandem GFP-mCherry-LC3 construct, sequestosome-1 (SQSTM1, P62) mRNA and protein levels, and autophagy-related gene (ATG) 5, 7, and 12 expression levels. The autophagic flux was evaluated as the ratio of yellow (autophagosomes) to red (autolysosomes) LC3 puncta. RESULTS: Following amino acid starvation, we found the LC3-II and ATG expression levels were enhanced in the IEC-18 cells. An increase in the number of autophagic vacuoles was concomitantly observed by TEM and confocal microscopy. Based on the results, supplementation with either alanine or proline depressed autophagy in the IEC-18 cells. Consistent with the elevated LC3-II levels, ATG expression increased upon NHE3 inhibition. Moreover, the mCherry-GFP-LC3 autophagic puncta representing both autophagosomes and autolysosomes per cell increased after EIPA treatment. CONCLUSIONS: These results demonstrate that NHE (most likely NHE3) may participate in the amino acid regulation of autophagy in IECs, which would aid in the design of better treatments for intestinal inflammation.

Effect of DHA supplements during pregnancy on the concentration of PUFA in breast milk of Chinese lactating mothers.

OBJECTIVE: To determine whether there is an effect of prenatal supplementation with docosahexaenoic acid (DHA) on the concentration of polyunsaturated fatty acids (PUFAs) in the breast milk of Chinese lactating women. METHODS: A total of 409 participants were recruited at the postpartum care center during their 1-month postpartum care. They were assigned to the supplement group or the control group according to whether or not DHA supplements were taken during pregnancy. Dietary intake was assessed with a food frequency questionnaire (FFQ). Breast milk samples were collected on 1 day between the 22nd and 25th day postpartum and levels of eight kinds of fatty acids in the breast milk were measured by gas chromatography. RESULTS: DHA intake was divided into three levels (<57 mg/day, 57-185 mg/day and >185 mg/day). The concentration of DHA postpartum in the breast milk of the group receiving a DHA supplement >185 mg/day was significantly higher (P=0.003) compared to the control group. CONCLUSIONS: DHA intake >185 mg/day resulted in increased DHA concentrations in breast milk. This finding suggests that mothers with inadequate dietary intake of DHA should change their dietary habits to consume a diet rich in DHA or take sufficient DHA supplements to meet the average nutritional needs of infants.

Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles.

Ultrafine aluminum oxide, which are abundant in ambient and involved occupational environments, are associated with neurobehavioral alterations. However, few studies have focused on the effect of sex differences following exposure to environmental Al2O3 ultrafine particles. In the present study, male and female mice were exposed to Al2O3 nanoparticles (NPs) through a respiratory route. Only the female mice showed depression-like behavior. Although no obvious pathological changes were observed in mice brain tissues, the neurotransmitter and voltage-gated ion channel related gene expression, as well as the small molecule metabolites in the cerebral cortex, were differentially modulated between male and female mice. Both mental disorder-involved gene expression levels and metabolomics analysis results strongly suggested that glutamate pathways were implicated in sex differentiation induced by Al2O3 NPs. Results demonstrated the potential mechanism of environmental ultrafine particle-induced depression-like behavior and the importance of sex dimorphism in the toxic research of environmental chemicals.

Relationships between degree of polymerization and antioxidant activities: a study on proanthocyanidins from the leaves of a medicinal mangrove plant Ceriops tagal.

Tannins from the leaves of a medicinal mangrove plant, Ceriops tagal, were purified and fractionated on Sephadex LH-20 columns. 13C nuclear magnetic resonance (13C-NMR), reversed/normal high performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI MS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDT-TOF MS) analysis showed that the tannins were predominantly B-type procyanidins with minor A-type linkages, galloyl and glucosyl substitutions, and a degree of polymerization (DP) up to 33. Thirteen subfractions of the procyanidins were successfully obtained by a modified fractionation method, and their antioxidant activities were investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and ferric reducing antioxidant power (FRAP) method. All these subfractions exhibited potent antioxidant activities, and eleven of them showed significantly different mean DP (mDP) ranging from 1.43±0.04 to 31.77±1.15. Regression analysis demonstrated that antioxidant activities were positively correlative with mDP when around mDP <10, while dropped and then remained at a level similar to mDP = 5 with around 95 µg ml(-1) for DPPH scavenging activity and 4 mmol AAE g(-1) for FRAP value.

Histologic comparison between platelet-rich plasma and blood clot in regenerative endodontic treatment: an animal study.

INTRODUCTION: In regenerative endodontic treatment (RET) for immature permanent tooth, better treatment results could be obtained by applying platelet-rich plasma (PRP) as the scaffold rather than the blood clot. The goal of this study was to compare the histologic differences between using PRP and blood clot in RET. METHODS: Three 6-month-old beagles each carrying 9 premolars with double root canals were randomly assigned to the PRP group, blood clot group, or negative control group. All experimental teeth suffered apical periodontitis, and RET was performed. In the blood clot group, bleeding was induced from the periapical tissues to fill the canal space. In the PRP group, autologous PRP was injected into each root canal. The animals were sacrificed 3 months later. Histologic sections were stained with hematoxylin-eosin. Statistical analysis was performed by the Fisher exact test, with the significance set at 0.05. RESULTS: With the ingrowth of cellular cementumlike tissues, the canal wall was thickened, and the apical apex was closed in both the PRP and blood clot groups. Cementocytelike cells were present in the newly formed tissues. Meanwhile, no statistical difference was found in both experimental groups for the average percentage of apical closure, new tissue formation, and pulplike tissue formation. Noticeably, a large number of inflammatory cells were present in some root canals in both groups although the postoperative radiograph revealed the disappearance of periapical radiolucency. CONCLUSIONS: PRP application could be an option for clinical cases in which little or no bleeding were found when irritating the apical tissue during RET.

α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

BACKGROUND: RNA interference (RNAi) has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC) therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment. METHODS: Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1) was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA) were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3) and non-HCC cell lines (L-02, Hela and SW1116) were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5) was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC) to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo. RESULTS: The AFP-miRNA system could silence target gene (Beclin 1) but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1) in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo. CONCLUSIONS: An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA) was successfully established. The system provides a usable tool for HCC-specific RNAi therapy, which may serve as a new treatment modality for HCC.

[The role of octahedral montone in colonic barrier protection in severe acute pancreatitis rat model.].

OBJECTIVE: To investigate the protective mechanism of octahedral montone in rats with acute pancreatitis. METHODS: Seventy-two SD rats were randomly divided into a sham-operation (SO) group, a severe acute pancreatitis (SAP) group and a treatment with octahedral montone group. Retrograde pancreatic ductal injection of 5% cholate sodium in rats was used to establish SAP models. Sham operation was done with intraperitoneal injection of normal saline. In the treated group octahedral montone was given through enema half hour before inducing SAP model. Then, we evaluate the pancreatic injury and detect the level of TNF-alpha, diamine oxidase (DAO) and endotoxin. Western blot and RT-PCR were used to determine the expressions of the tight junction protein occludin in the endothelial cells of intestinal mucosa at the time of hour 3, 6, 12 after operation. RESULTS: (1) The pathological scores of pancreatitis were significantly higher in the SAP group than those in the treatment group and SO group (P < 0.05). (2) Compared with the SO group, the level of TNF-alpha in the SAP group and the treatment group was much higher (P < 0.05), but the level in the treatment group was lower than that in the SAP group (P < 0.05). (3) The serum concentration of DAO and endotoxin was significantly increased in the SAP group, and the concentration in treatment group was higher than that in the SO group (P < 0.01), but lower than that in the SAP group (P < 0.01). The occludin protein and mRNA expression in the SAP group was the lowest and the expression in the treatment group was higher than that in the SAP group (P < 0.01), but lower than that in the SO group (P < 0.01). CONCLUSIONS: Octahedral montone can improve the colonic barrier function, reduce the endotoxemia, and ameliorate the inflammation during acute pancreatitis.

[Construction of recombinant adenovirus for the angiogenic inhibitor, vasostatin, and its expression in vitro].

OBJECTIVE: To construct a recombinant replication-deficient adenovirus for the angiogenic inhibitor, vasostatin and assay its expression in vitro. METHODS: The cDNA for vasostatin was got by PCR amplification, then it was cloned into T vector and confirmed by enzymatic analysis and direct sequencing. Subsequently the cDNA was subcloned into the shuttle plasmid, and co-transformed into 293 cells with backbone plasmid. The resulting recombinant andenovirus was confirmed by PCR and western blot. The activity was assayed by inhibition of HUVEC growth. RESULTS: The PCR product was about 590 bp in length, and sequencing result was identical to that reported. The construction of recombinant replication-deficient adenovirus was confirmed by PCR. Western blot analysis showed the expression of vasostatin in vitro. The supernatant from transduced HeLa cells inhibited the growth of HUVEC specifically. CONCLUSION: The recombinant adenovirus for vasostatin efficiently mediated the expression of the protein in vitro.

Field population-based blocking treatment of esophageal epithelia dysplasia.

AIM: To confirm the value of blocking treatment by zenshengping (ZSP), a Chinese herb composite, and Riboflavin for esophageal epithelia dysplasia cases screened out in high risk area in northern china by exfoliative balloon cytology (EBC), so to reduce the incidence rate of esophageal cancer(EC). METHODS: Esophageal epithelium dysplasia cases including mind esophageal epithelium dysplasia (MEED), stage one severe esophageal epithelium dysplasia (SEED I), and stage two severe esophageal epithelium dysplasia (SEED II) were screened out from people aged 40 years and older in the high risk area of Chixian. These cases were randomly divided into a treatment and control group. Subjects in the treatment and control groups took ZSP, riboflavin, and placebo daily for three years. EC cases registered by cancer registry and identified by EBC re-screening in the treatment and control groups were used to calculate incidence and blocking rates to demonstrate the effects of blocking medication. RESULTS: It was found that 31.92% and 24.15% of people aged 40 years and older in Cixian could been diagnosed as MEED and SEED cases. The severity of dysplasia increased with age. ZSP had blocked EC occurrence by 47.79% after 3 year medication among the SEED cases. CONCLUSION: ZSP can block the development from SEED I and SEED II to EC by 47.79%. Efforts should be made to screen and treat dysplasia cases in people aged 40 years and older in high risk areas to reduce the mortality figures.