Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study.

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

Industrial-scale composting of swine manure with a novel additive-yellow phosphorus slag: Variation in maturity indicators, compost quality and phosphorus speciation.

Composting experiment of swine manure, adding with yellow phosphorus slag(YPS) at 5% (w/w), was conducted in an industrial-scale reactor covered with semi-permeable membrane. During 27 days of composting, the changes in temperature, compost quality and phosphorus(P) speciation of products were monitored. Results indicated that the temperature of compost pile was sharply increased on day 2, and the thermophilic period lasted for 15 days. The dynamics in germination index(GI), pH, nutrient contents, etc. of products were in line with conventional composting process. For P distribution, the contents of total-P and citric acid extracted-P(CAP) of products were increased during composting, while that of Olsen-P was decreased. HCl extracted inorganic P(HCl-Pi), a slowly release fraction of P, was dominated in the product, which showed an increasing trend during the composting. These results suggest that the industrial-scale composting with novel YPS additive can be accomplished, and its product contains abundant slowly released P.

BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy.

Precision medicine urges the development of theranostics which can efficiently integrate precise diagnosis and effective therapy. In this study, a facile synthesis of Ir/Gd bimetallic oxide nanotheranostics (termed BSA@Gd2O3/IrO2 NPs) with good biocompatibility was demonstrated using a biomineralization method where bovine serum albumin (BSA) served as a versatile template. BSA@Gd2O3/IrO2 NPs exhibited high longitudinal relaxivity (5.2 mM-1 s-1) and X-ray absorption capability (14.5 Hu mM-1), illustrating them to be a good contrast agent for magnetic resonance (MR) and computed tomography (CT) dual-modal imaging. Moreover, BSA@Gd2O3/IrO2 NPs can act as not only a photothermal conversion agent with ultrahigh efficiency (66.7%) as well as a good photosensitizer, but also an effective catalase to decompose endogenous H2O2 to produce O2, thus relieving hypoxia and enhancing the phototherapeutic effect. Both in vitro and in vivo experiments demonstrated the high effectiveness of BSA@Gd2O3/IrO2 NPs in MR/CT dual-modal imaging and photothermal and photodynamic synergistic tumor treatments. This work sheds new light on the development of versatile nanotheranostic systems using mild and robust biomineralization methods.

Effectiveness and safety of treating carotid atherosclerotic plaques with the method of nourishing qi, promoting blood circulation and expelling phlegm: A systematic review and meta-analysis.

Objectives: This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm (YQHXZT), in treating carotid atherosclerosis (CAS) from an immunological perspective. Background: The incidence of CAS has been increasing and tends to be younger. Although western medicine is effective, there are some limitations. TCM has certain advantages over the multichannel and multitarget treatment strategies in slowing down the process of CAS. However, there is no comprehensive review in this field. Methods: Nine databases were searched from January, 2012, to September, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed. The GRADE was used to assess the quality of the evidence. Results: Fourteen RCTs involving 1,191 patients were identified. The results indicated that the experimental group was more effective in improving carotid intima-media thickness (CIMT)[SMD = -0.97, 95%CI(-.30,-0.65), p < 0.00001], reducing carotid plaque area [SMD = -1.98, 95%CI(-3.06,-0.89), p = 0.0003], lowering hs-CRP [SMD = -1.33, 95%CI(-1.59,-1.06), p < 0.00001] and LDL-C levels [SMD = -0.60, 95%CI(-0.83,-0.38), p < 0.00001]. Moreover, the experimental group was superior to peak systolic blood flow velocity (PSV) [SMD = -0.37, 95%CI(-0.59,-0.16), p = 0.0007], clinical efficacy [RR = 1.64, 95% CI (1.39, 1.94), p < 0.00001] and plaque area efficacy [RR = 1.36, 95% CI (1.22, 1.52), p < 0.0001]. The adverse reactions were not statistically significant in the two groups [RD = -0.01, 95% CI (-0.04.0.01), p = 0.17]. The results of grade evaluation suggested that the outcome indicators LDL-C, hs-CRP, plaque area efficacy, PSV, and adverse events were moderate. CIMT, plaque reduction area, and TCM clinical efficacy were low-quality. Conclusion: The combination of YQHXZT can alleviate the process of CAS by inhibiting the thickening of CIMT, reducing plaque area and lowering hs-CRP and LDL-C levels. The mechanism may possibly be related to reducing lipid deposition and inhibiting the inflammatory response. Besides, the combination did not increase the risk of adverse effects. However, more well-designed RCTs are needed in the future. Systematic review registration: CRD42022360529, https://www.crd.york.ac.uk/prospero/.

Vitexin attenuates autoimmune hepatitis in mouse induced by syngeneic liver cytosolic proteins via activation of AMPK/AKT/GSK-3ß/Nrf2 pathway.

Autoimmune hepatitis (AIH) is a chronic progressive liver disease that currently does not have a successful therapeutic option. Vitexin, a bioflavonoid isolated from various medicinal plants, possesses a variety of activities; however, whether vitexin protects against AIH remains unclear. Therefore, the current study aims to investigate the hepatoprotective effects and mechanism of action of vitexin in both an experimental autoimmune hepatitis (EAH) mouse model and in D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatocyte injury. Syngeneic liver antigen S100 was used to establish EAH. Vitexin treatment significantly decreased the infiltration of inflammatory and CD4+ T cells in the liver, reduced ALT and AST levels in the serum and attenuated hepatic injury due to oxidative stress. Moreover, vitexin mitigated the upregulation of Bax and cleaved caspase-3 and the downregulation of Bcl-2 in the livers of AIH mice. These regulations were accompanied by not only increased phosphorylation of AMPK, AKT and GSK-3ß but also activation of Nrf2. Furthermore, vitexin inhibited apoptosis and the overexpression of inflammatory cytokines in D-GalN/LPS-treated AML12 cells. In addition, vitexin enhanced the phosphorylation of AMPK, AKT and GSK-3ß. When AML12 cells were treated with an inhibitor of AMPK/AKT or specific siRNA targeting Nrf2, vitexin did not further induce the activation of Nrf2/HO-1. A molecular docking study confirmed that vitexin could interact with AMPK through hydrogen bonding interactions. In conclusion, vitexin ameliorated hepatic injury in EAH mice through activation of the AMPK/AKT/GSK-3ß pathway and upregulation of the Nrf2 gene.

Cause-specific mortality of low and selective intermediate-risk prostate cancer patients with active surveillance or watchful waiting.

BACKGROUND: Active surveillance or watchful waiting (AS/WW) is increasingly being used as an alternative strategy to radical prostatectomy or radiation therapy for appropriately selected patients with prostate cancer (PCa). However, the prognosis of low-risk and selective intermediate-risk PCa patients after AS/WW is poorly defined. In this study we reviewed the patients registered in the Surveillance, Epidemiology, and End Results (SEER) Program to establish a competing risk nomogram for the prediction of prostate cancer-specific mortality (PCSM). METHODS: The information of patients undergoing AS/WW in the SEER program from 2004 to 2015 was obtained. All patients were ISUP (International Society of Urological Pathology) grade 1 or 2 PCa and also fulfilled the National Comprehensive Cancer Network's definition of low-risk PCa [prostate specific antigen (PSA) <10 ng/mL and cT2aN0M0 or less)]. A competing risk nomogram was used to analyze the association of tumor characteristics with PCSM and non-PCSM among the PCa patients with AS/WW. All cases were randomly divided into a training cohort and a validation cohort (1:1). A competing risk nomogram was constructed to predict PCSM in PCa patients with AS/WW. The performance of the PCSM nomogram was evaluated using the concordance index (C-index) and calibration curve. RESULTS: A total of 30,538 PCa patients were identified as low risk or selective intermediate risk with AS/WW. The 10-year cumulative incidence of death from prostate cancer and death from other cause were 2.8% (95% CI: 2.4-3.1%) and 19.3% (95% CI: 17.8-20.5%), respectively. Variables associated with PCSM included age, marital status, PSA, and ISUP grade. The PCSM nomogram had a good performance in both the training and validation cohorts, with a C-index of 0.744 (95% CI: 0.700-0.781, P<0.001) and 0.738 (95% CI: 0.700-0.777, P<0.001), respectively. CONCLUSIONS: Overall, the prognosis was favorable for the low- and selective intermediate-risk PCa patients with AS/WW. The competing risk nomogram yielded a good performance in identifying subgroups of patients with a higher risk of PCSM and potential candidates for AS/WW.

The Immunomodulatory Activity of Polysaccharides from the Medicinal Mushroom Amauroderma rude (Agaricomycetes) Is Mediated via the iNOS and PLA2-AA Pathways.

Our earlier work indicated that the polysaccharides of Amauroderma rude (AR) appear to have an effect on immunoregulation. However, the pathways are not clear. In this paper, we discuss the immunomodulatory mechanisms of A. rude to provide a scientific basis for its possible use as a food. Amauroderma rude increased the expression of iNOS and P38 in the Raw246.7 cell line. When the AR concentration reached 150 µg/mL, the expressions of iNOS and P38 increased 23.0% and 191.7%, respectively. When the AR concentrations were 50 µg/mL, the concentrations of cytokines IL-2, TNF-α, and IFN-γ were 33.65 pg/mL, 12.53 pg/mL and 42.56 pg/mL. When AR reached 200 µg/mL, the lgA and lgM levels were 0.73 µg/mL and 1.5 µg/mL. When AR reached 400 µg/mL, the lgG level reached 1.65 µg/mL by ELISA assay. When 4.8 mg AR were orally administered, IL-2, TNF-α, IFN-γ, PGE2, and LTB4 increased dramatically, to 0.17 pg/mL, 0.16 pg/mL, 0.15 pg/mL, 30.71 pg/mL, and 18.68 pg/mL, respectively. The concentrations of lgA, lgM, and lgG, AA, and PLA2 also increased significantly to 2.62 pg/mL, 2.14 pg/mL, 2.06 pg/mL, 5.23 µg/mL and 3.68 ng/mL, respectively. With 4.8 mg AR p.o., iNOS protein expression increased 16.8% and P38 increased 234.0%. These results indicate that A. rude polysaccharides stimulate cytokine production and activate the iNOS, PLA2-AA, and MAPK pathways during the immunomodulatory process.

[Electroacupuncture of Hegu(LI 4) and Sanyinjiao(SP 6) Assists Medicinal Abortion].

OBJECTIVE: To observe the effectiveness of electroacupuncture (EA) therapy in promoting medicinal abortion. METHODS: Sixty participants with early pregnancy were randomly divided into medication (control) and EA+ medication groups (n=30 in each). Participants in the control group were treated by regular medication (mifepristone and misoprostol tablets), and those of the EA group were treated by EA stimulation (2 Hz/100 Hz, a tolerable strength) of bilateral Hegu(LI 4) and Sanyinjiao(SP 6) for 25 min, and also by the same medication method mentioned in the control group. Participants of both groups were admitted to the hospital for observation on the 3rd day after taking medication. The abdominal pain was assessed by visual analogue scale (VAS) score, and the foetal sac discharge duration and the complete abortion rate were recorded. RESULTS: After the treatment, the VAS scores of both groups were significantly reduced in comparison with their own pre-treatment in each group (P<0.01), and the VAS score of the EA+ medication group was significantly lower than that of the medication group (P<0.01). The foetal sac discharge duration was significantly shorter in the EA+ medication group than in the medication group (P<0.01). The abortion rates showed no significant difference between the two groups (P>0.05). CONCLUSION: EA stimulation of Hegu(LI 4) and Sanyinjiao(SP 6) has a positive effect in assisting medicinal abortion in reducing abdominal pain and shortening foetal sac discharge duration.

Dietary Polysaccharide from Enteromorpha Clathrata Modulates Gut Microbiota and Promotes the Growth of Akkermansia muciniphila, Bifidobacterium spp. and Lactobacillus spp.

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.

Structural modulation of gut microbiota by chondroitin sulfate and its oligosaccharide.

Chondroitin sulfate (CS) as a dietary supplement and a symptomatic slow acting (SYSA) drug has been used for years. Recently, CS has been demonstrated to be readily degraded and fermented in vitro by specific human gut microbes, hinting that dietary CS may pose a potential effect on gut microbiota composition in vivo. However, until now, little information is available on modulations of gut microbiota by CS. In the present study, modulations of gut microbiota in Kunming mice by CS and its oligosaccharide (CSO) were investigated by high-throughput sequencing. As evidenced by Heatmap and principal component analysis (PCA), the female microbiota were more vulnerable than the male microbiota to CS and CSO treatment. Besides, it is of interest to found that CS and CSO had differing effects on the abundance of Bacteroidales S24-7, Bacteroides, Helicobacter, Odoribacter, Prevotellaceae and Lactobacillus in male mice versus female mice. Collectively, we demonstrated a sex-dependent effect on gut microbiota of CS and CSO. In addition, since gut microbiota exerts a major effect on host physiology, our study highlighted that certain beneficial effects of CS may be associated with modulations of gut microbiota, which merits further investigation.

[Predicting value of dynamic alteration of blood neutrophil/lymphocyte ratio on recurrence-free survival in patients with advanced colon cancer after operation and chemotherapy].

OBJECTIVE: To evaluate whether neutrophil-lymphocyte ratio(NLR) predicts risk of recurrence in patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy. METHODS: A total of 149 patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy(FOLFOX6 protocol) were included. NLR was calculated preoperatively and before chemotherapy. The changes in NLR and the predictive value of NLR for prognosis were analyzed. RESULTS: The NLR of 149 patients was 2.8±1.5. NLR of 3.5 was identified according to the ROC curve. NLR<3.5 and NLR≥3.5 were classified as low and high NLR group, respectively. The 5-year recurrence-free survival(RFS) of patients with high preoperative NLR(n=22) was significantly worse than that of those with low preoperative NLR(n=127)(50.9% vs. 76.4%, P=0.025). The difference of 5-year RFS between high pre-chemotherapy NLR group(n=34) and low pre-chemotherapy NLR group(n=115) was statistically significant(50.1% vs. 71.4%, P=0.032). The 5-year RFS was 79.5% in patients with low preoperative NLR converting to high pre-chemotherapy NLR(n=16), similar to the group with high pre-chemotherapy group(P=0.077). The 5-year RFS was 17.7% in patients with high preoperative NLR reverting to low pre-chemotherapy NLR(n=12), similar to the group with low pre-chemotherapy group(P=0.978). There was significant difference in 5-year RFS between the postoperatively elevated group and postoperatively decreased group(P=0.036). CONCLUSION: An elevated blood NLR may be a biomarker of poor RFS in patients with advanced colon cancer after curative resection and chemotherapy.

Cortical microtubule labeling: insight of AFH14 in non-dividing cells.

We recently reported that AFH14 participated in microtubule and actin filament interaction in cell division, and the AFH14 (FH1FH2) was important to the directly binding activity of microtubules and microfilaments. To preliminarily understand the function and localization of AFH14 in non-dividing cells, we overexpressed FH1FH2-RFP in onion epidermal cells, and found a fluorescence labeled filamentous network. The result of double labeling with different cytoskeleton reporter proteins indicated that FH1FH2-RFP co-localized with cortical microtubules. Treatment of cells expressing FH1FH2-RFP with cytoskeleton disrupting drugs confirms that FH1FH2-RFP binds to microtubules. Moreover, the binding of FH1FH2-RFP to microtubules were revealed to be dynamic by fluorescence recovery after photobleaching (FRAP) experiment. Time-lapse confocal microscopy showed that FH1FH2-RFP could display a dynamics similar to the microtubule dynamic instability. These data suggest that FH1FH2 domain may lead AFH14 function on cortical microtubules in non-dividing cells, and FH1FH2-RFP may be utilized as a microtubule reporter protein in living onion epidermal cells.