Efficacy and Safety Factors Related to Plasma Concentration-Optimized Polymyxin B Therapy in Treating Carbapenem-Resistant Gram-Negative Bacterial Infections in China.

Background: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety. Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis. Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035-12.727; P = 0.044), Cmin greater than 2.3 µg/mL (OR: 7.37; 95% CI: 1.571-34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732-51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139-152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 µg/mL and AUC = 82.0 mg h/L. Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 µg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.

Detection technology and clinical applications of serum viral products of hepatitis B virus infection.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

First-principle calculations study of the ORR/OER electrocatalytic activity of ruthenium polyphthalocyanine axially modified with aliphatic thiol groups.

In this study, the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activity of ruthenium polyphthalocyanine axially modified with different aliphatic thiol groups, RuPPc-SR (SR = -SCH3, -SC2H5, -SC3H7, -SC4H9, -SC5H11, and -SC6H13), in an acidic medium were simulated using DFT. All -SR groups can effectively enhance the ORR and OER catalytic activities of RuPPc. The ORR and OER overpotentials of RuPPc-SC4H9 are 0.237 V and 0.436 V, respectively, which are far lower than those of RuPPc (0.960 V and 0.903 V). For RuPPc-SC4H9, the four C and S atoms of the -SC4H9 chain and Ru atom are coplanar, and thus, conjugate effects and inductive effects exist between the -SC4H9 chain and Ru atom. This makes the Ru atom exhibit the least positive Bader charge and smallest spin density, and the anti-bonding orbitals of dxz, dyz, and dz2 of the Ru atom shift below the Fermi level (Ef). This makes the adsorption strength of RuPPc-SC4H9 toward ORR and OER intermediates the weakest, which accelerates the reaction process, thus resulting in better ORR and OER catalytic activity. Therefore, the introduction of the aliphatic thiol groups might effectively improve the OER/ORR catalytic activity of RuPPc.

Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

Scanning the latent phases and superconductivity in the Nb-Pb system at high pressure.

So far, few literature studies have been reported on niobium-lead binary intermetallic compounds, which are expected to have very different properties compared to existing niobium-carbon binary compounds, due to the distinct electronic properties of lead when compared to other carbon-group elements. Herein, we carry out a global structure search for the Nb-Pb system based on the evolutionary algorithm and density functional theory. Based on the dynamical and mechanical stability analyses, we unveiled five new phases, P4/m-Nb9Pb, Cmcm-Nb3Pb, I4/mmm-Nb2Pb, Pmm2-Nb5Pb3, and I4/mmm-NbPb2, that are promising candidates for experimental synthesis. Moreover, the superconducting transitions of all Nb-Pb binary intermetallic compounds are performed with electron-phonon calculations. As Nb9Pb exhibited the maximum Tc in the Nb-Pb intermetallics, greater than 3.0 K at 20 GPa, the phonon band structures, partial phonon density of states (PHDOS), the corresponding Eliashberg spectral functions α2F(ω), and integral electron-phonon coupling (EPC) parameters λ as a function of frequency of Nb9Pb were also studied. This work filled the gap in the pressure-tuned Nb-Pb phase transitions from a systematic first principles study for the first time.

The effect of acupoint catgut embedding and drug therapy on hyperlipidemia: a meta-analysis of randomized controlled trials.

There is no consensus on whether acupoint catgut embedding should be widely used as a treatment for hyperlipidemia. Acupoint catgut embedding is also not included in the guidelines for the treatment of hyperlipidemia. The purpose of this study was of two aspects: 1) to review recent research advances in the relationship between acupoint catgut embedding and hyperlipidemia, 2) to make a meta-analysis of the effects of acupoint catgut embedding on hyperlipidemia. We conducted a meta-analysis of studies extracted from PubMed, the Cochrane Library, Embase CNKI, Wanfang Data and VIP to identify randomized controlled trials (RCTs) evaluating the efficacy of acupoint catgut embedding on hyperlipidemia evaluated through screening, inclusion, data extraction and quality assessment. We performed a meta-analysis using Review Manager 5.3 software. A total of 9 RCTs, involving more than 500 adults over 18 years old, were included. Compared with acupoint catgut embedding, drugs resulted in TC [MD = -0.08, 95% CI (-0.20, 0.05), p = 0.41, I2 = 2%], in TG [MD =-0.04, 95% CI (-0.20, 0.11), p = 0.09, I2 = 43%], in HDL-C [MD = 0.02, 95% CI (-0.12, 0.16), p = 0.07, I2 = 50%], in LDL-C [MD = 0.16, 95% CI (0.02, 0.29), p = 0.17, I2 = 34%]. Based on the current evidence, acupoint catgut embedding is not significantly more effective than drugs in reducing hyperlipidemia. More randomized trials are needed to confirm this conclusion.

Extensive heterotopic pancreas in a rare site: A case report and a review of literature.

RATIONALE: Heterotopic pancreas is a pancreatic tissue that occurs outside the normal anatomical site, the most common site is antrum. Due to the lack of specific imaging and endoscopic signs, heterotopic pancreas especially those occurring in the rare site, are often misdiagnosed, and leading to unnecessary surgical treatment. Endoscopic incisional biopsy and endoscopic ultrasound-guided fine-needle aspiration are effective means for diagnosing heterotopic pancreas. We reports a case of extensive heterotopic pancreas in a rare site, which was finally diagnosed by this way. PATIENT CONCERNS: A 62-year-old man was admitted due to the presence of an angular notch lesion, which was suspected as gastric cancer before. He denied any history of tumor or gastric disease. DIAGNOSES: No abnormality was found in the physical examination and laboratory testing after admission. Computed tomography showed localized thickening of the gastric wall measuring 30 mm in the long diameter. Gastroscope revealed a nodular-like submucosal protuberance at the angular notch with size of about 3*4 cm. Ultrasonic gastroscope showed that the lesion was located in the submucosa. The lesion exhibited mixed echogenicity. The diagnosis can not be identified. INTERVENTIONS: 2 times of incision biopsy were performed to make a clear diagnosis. Finally, appropriate tissue specimens were obtained for pathology testing. OUTCOMES: The patient was diagnosed as heterotopic pancreas according to pathology. He was recommended to undergo observation and regular follow-ups rather than surgery. Then he was discharged home with no discomfort. LESSONS: Heterotopic pancreas occurring in the angular notch is extremely rare, the site is scarcely reported in the relevant literature. Therefore, it is easy to be misdiagnosed. In the cases of an vague diagnosis, endoscopic incisional biopsy or endoscopic ultrasound-guided fine-needle aspiration may be a good choice.

A mediated moderation model of negative life events, self-esteem, rumination and parental divorce on depression among Chinese juvenile delinquents.

Little attention was paid to the prevalence of depression in Chinese juvenile delinquents who are studied in correctional work-study schools. Hence, the present study aimed to test the unique, mediating and moderating effects of negative life events, self-esteem, rumination and parental divorce on depression among Chinese juvenile delinquents. A total of 236 juvenile delinquents aged between 12 and 17 years old (M = 14.68 SD = 1.30) were recruited to accomplish a battery of self-report questionnaires concerning their negative life events, self-esteem, rumination, depression and demographic profile. The descriptive analysis showed that there was a positive correlation between negative life events and depression in Chinese juvenile delinquents. Moreover, the results from the structural model indicated that self-esteem and rumination played separate and sequential mediating roles between negative life events and depression. In addition, parental divorce had a moderating effect between negative life events and self-esteem in the model. These results suggest that the prevalence of depression among Chinese juvenile delinquents can be reduced through modification of the ruminative way of thinking, improving their self-esteem when they encounter a number of negative life events. Furthermore, more attention should be paid to the juvenile delinquents who experienced parental divorce.

Theoretical Study on ORR/OER Bifunctional Catalytic Activity of Axial Functionalized Iron Polyphthalocyanine.

Designing efficient ORR/OER bifunctional electrocatalysts is very significant for reducing energy consumption and environmental protection. Hence, we studied the ORR/OER bifunctional catalytic activity of iron polyphthalocyanine (FePPc) coordinated by a series of axial ligands which has different electronegative coordination atom (FePPc-L) (L = -CN, -SH, -SCH3, -SC2H5, -I, -Br, -NH2, -Cl, -OCH3, -OH, and -F) in alkaline medium by DFT calculations. Among all FePPc-L, FePPc-CN, FePPc-SH, FePPc-SCH3, and FePPc-SC2H5 exhibit excellent ORR/OER bifunctional catalytic activities. Their ORR/OER overpotential is 0.256 V/0.234 V, 0.278 V/0.256 V, 0.280 V/0.329 V, and 0.290 V/0.316 V, respectively, which are much lower than that of the FePPc (0.483 V/0.834 V). The analysis of the electronic structure of the above catalysts shows that the electronegativity of the coordination atoms in the axial ligand is small, resulting in less distribution of dz2, dyz, and dxz orbitals near Ef, weak orbital polarization, small charge and magnetic moment of the central Fe atom, and weak adsorption strength for *OH. All these prove that the introduction of axial ligands with appropriate electronegativity coordinating atoms can adjust the adsorption of catalyst to intermediates and modify the ORR/OER bifunctional catalytic activities. This is an effective strategy for designing efficient ORR/OER bifunctional electrocatalysts.

Understanding the Potential Gene Regulatory Network of Starch Biosynthesis in Tartary Buckwheat by RNA-Seq.

Starch is a major component of crop grains, and its content affects food quality and taste. Tartary buckwheat is a traditional pseudo-cereal used in food as well as medicine. Starch content, granule morphology, and physicochemical properties have been extensively studied in Tartary buckwheat. However, the complex regulatory network related to its starch biosynthesis needs to be elucidated. Here, we performed RNA-seq analyses using seven Tartary buckwheat varieties differing in starch content and combined the RNA-seq data with starch content by weighted correlation network analysis (WGCNA). As a result, 10,873 differentially expressed genes (DEGs) were identified and were functionally clustered to six hierarchical clusters. Fifteen starch biosynthesis genes had higher expression level in seeds. Four trait-specific modules and 3131 hub genes were identified by WGCNA, with the lightcyan and brown modules positively correlated with starch-related traits. Furthermore, two potential gene regulatory networks were proposed, including the co-expression of FtNAC70, FtPUL, and FtGBSS1-3 in the lightcyan module and FtbHLH5, C3H, FtBE2, FtISA3, FtSS3-5, and FtSS1 in the brown. All the above genes were preferentially expressed in seeds, further suggesting their role in seed starch biosynthesis. These results provide crucial guidance for further research on starch biosynthesis and its regulatory network in Tartary buckwheat.

Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota.

Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2-3°months old) and old-FMT-group transplanted from old donors (10-11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.

Platycodon grandiflorus polysaccharides deeply participate in the anti-chronic bronchitis effects of platycodon grandiflorus decoction, a representative of "the lung and intestine are related".

Platycodon grandiflorus (Jacq.) A. DC. (PG) root is one of the most commonly used medicine-food materials for respiratory discomfort in Asia, usually in the form of a decoction or leaching solution. As everyone knows, both of decoction and leaching solution is a polyphase dispersion system, containing low-molecular-weight water-soluble active ingredients and hydrophilic macromolecules. This study aimed to discuss the synergistic effect of Platycodon grandiflorus polysaccharide (PGP) and platycodin D (PD) in PG decoction against chronic bronchitis (CB) and the mechanism underlying. A series of PGP, PD, and PGD + PD suspensions were administrated to CB model rats, on the levels of whole animal and in situ intestinal segment with or without mesenteric lymphatic vessels ligation. It exhibited that PGP exhibited synergistic effects with PD, on improving the histopathological abnormity, mucus secretion excess, and immunological imbalance in lung of CB model rat, closely associated with its modulations on the mucosal immunity status in small intestine. The polysaccharide macromolecules in PG decoction or leaching solution should be responsible for the modulation of pulmonary immune state, possibly through the common mucosal immune between small intestine and lung. These results might be a new perspective that illustrates the classical theory of "the lung and intestine are related" in traditional Chinese medicine.

Coptis chinensis polysaccharides dynamically influence the paracellular absorption pathway in the small intestine by modulating the intestinal mucosal immunity microenvironment.

BACKGROUND: Traditional Chinese Medicine decoctions (TCMDs) can be used to prepare outstanding pharmaceutical preparations by the patient themselves. Small molecular active ingredients and macromolecular polysaccharides are inevitably co-existed in TCMDs. Different from the pharmacological synergies among small molecules, the macromolecular polysaccharides in TCMDs might contribute to disease treatment in several ways, although it is frequently overlooked. HYPOTHESIS/PURPOSE: This study proposes that the oral bioavailability of the water-insoluble alkaloids of Coptis chinensis Franch. (Ranunculaceae) (C. chinensis) decoction may be attributed to the co-existing C. chinensis polysaccharides (CCPs) dynamically influencing the small intestine microenvironment and regulating the modulation of the paracellular absorption pathway. METHODS: First, the effects of CCPs on the oral bioavailability of the main active ingredient of C. chinensis, berberine, were evaluated in vivo. Next, a series of in situ experimental models of intestinal perfusion and models of isolated jejunal mucosa, Caco-2 cell monolayer membranes, and microfold-like cells were established to assess the correlation among CCPs, intestinal mucosal immunity, and paracellular absorption in the small intestine. RESULTS: It was observed that CCPs could be endocytosed by the microfold cells on the surface of Peyer's patches, allowing CCPs to activate the lymphocytes, modulate the balance of Th1/Th2, control the secretion of immune effectors IFN-γ and IL-4, and finally regulate the tight junctions in the intestinal epithelial cells. This was a dynamic process with the movement of CCPs in the gastrointestinal tract that altered the flora distribution and functioning of the TLR/NF-κB signal pathway in the small intestine. CONCLUSION: The dynamical regulation of CCP on the immune microenvironment of small intestine is responsible for its promotion on the health controlling effects of C. chinensis in traditional dosage forms of decoction.

Integrated Transcriptomics and Widely Targeted Metabolomics Analyses Provide Insights Into Flavonoid Biosynthesis in the Rhizomes of Golden Buckwheat (Fagopyrum cymosum).

Golden buckwheat (Fagopyrum cymosum) is used in Traditional Chinese Medicine. It has received attention because of the high value of its various medicinal and nutritional metabolites, especially flavonoids (catechin and epicatechin). However, the metabolites and their encoding genes in golden buckwheat have not yet been identified in the global landscape. This study performed transcriptomics and widely targeted metabolomics analyses for the first time on rhizomes of golden buckwheat. As a result, 10,191 differentially expressed genes (DEGs) and 297 differentially regulated metabolites (DRMs) were identified, among which the flavonoid biosynthesis pathway was enriched in both transcriptome and metabolome. The integration analyses of the transcriptome and the metabolome revealed a network related to catechin, in which four metabolites and 14 genes interacted with each other. Subsequently, an SG5 R2R3-MYB transcription factor, named FcMYB1, was identified as a transcriptional activator in catechin biosynthesis, as it was positively correlated to eight flavonoid biosynthesis genes in their expression patterns and was directly bound to the promoters of FcLAR2 and FcF3'H1 by yeast one hybrid analysis. Finally, a flavonoid biosynthesis pathway was proposed in the rhizomes of golden buckwheat, including 13 metabolites, 11 genes encoding 9 enzymes, and 1 MYB transcription factor. The expression of 12 DEGs were validated by qRT-PCR, resulting in a good agreement with the Pearson R ranging from 0.83 to 1. The study provided a comprehensive flavonoid biosynthesis and regulatory network of golden buckwheat.

Identification of novel biomarkers for sepsis diagnosis via serum proteomic analysis using iTRAQ-2D-LC-MS/MS.

BACKGROUND: Sepsis is a common cause of morbidity and mortality in the ICU patients. Early diagnosis and appropriate patient management is the key to improve the patient survival and to limit disabilities in sepsis patients. This study was aimed to find new diagnostic biomarkers of sepsis. METHODS: In this study, serum proteomic profiles in sepsis patients by iTRAQ2D-LC-MS/MS. Thirty seven differentially expressed proteins were identified in patients with sepsis, and six proteins including ApoC3, SERPINA1, VCAM1, B2M, GPX3, and ApoE were selected for further verification by ELISA and immunoturbidimetry in 53 patients of non-sepsis, 37 patients of sepsis, and 35 patients of septic shock. Descriptive statistics, functional enrichment analysis, and ROC curve analysis were conducted. RESULTS: The level of ApoC3 was gradually decreased among non-sepsis, sepsis, and septic shock groups (p = 0.049). The levels of VCAM1 (p = 0.010), B2M (p = 0.004), and ApoE (p = 0.039) were showing an increased tread in three groups, with the peak values of B2M and ApoE in the sepsis group. ROC curve analysis for septic diagnosis showed that the areas under ROC curve (AUC) of ApoC3, VCAM1, B2M, and ApoE were 0.625, 0.679, 0.581, and 0.619, respectively, which were lower than that of PCT (AUC 0.717) and CRP (AUC 0.706), but there were no significant differences between each index and PCT or CRP. The combination including four validated indexes and two classical infection indexes for septic diagnosis had the highest AUC-ROC of 0.772. CONCLUSION: Proteins of ApoC3, VCAM1, B2M, and ApoE provide a supplement to classical biomarkers for septic diagnosis.

Laser speckle contrast imaging to monitor microcirculation: An effective method to predict outcome in patients with sepsis and septic shock.

Background: This study examines the microcirculation of patients with sepsis and septic shock using Laser Speckle Contrast Imaging (LSCI) technology, to enhance monitoring and predict outcomes of sepsis and septic shock. Methods: From 01 July 2021, to 31 January 2022, 44 patients diagnosed with septic shock and sepsis were included in the study, their clinical data were collected, and LSCI was used to monitor the mean peripheral blood flow perfusion index (PI). Results: The average peripheral blood flow PI of septic shock patients was significantly lower than that of septic patients, with a cutoff value of 26.25. The average peripheral blood flow PI negatively correlated with acute physiology and chronic health evaluation (APACHE) Ⅱ score (p = .01 < .05), sequential organ failure assessment (SOFA) score (p < .01), and lactic acid levels (p = .01 < .05). We report average peripheral blood flow no correlation with age, mean arterial pressure, body temperature, oxygen saturation, heart rate, and body mass index. There was no correlation with procalcitonin, C-reactive protein (CRP), red blood cell distribution width, or platelet distribution width (p > .05). PI significantly correlated with the group sepsis and septic shock (p < .001, r = -.865). And PI significantly correlated with the outcome or mortality (p = .007 < .05, r = -.398). The ROC curve was calculated for PI and the sensitivity was 81.3%, and the specificity was 75% when PI cutoff value chooses 20.88. Conclusion: LSCI technology successfully detected the fingertip microcirculation of patients with septic shock. LSCI can reliably differentiate patients with sepsis vs patients with septic shock. Additionally, the average peripheral blood PI negatively correlated with APACHE Ⅱ, SOFA score, and lactate acid levels, providing useful and supplementary information for the diagnosis and monitoring of septic shock. Trial registration: Chictr2100046761. Registered on May 28, 2021. Clinical Trial Registration: clinicaltrials.gov, identifier Chictr2100046761.

Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria.

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.