[Recent advances in metabolic engineering of microorganisms for production of tyrosol and its derivatives].

Tyrosol is a natural phenolic compound with antioxidant, anti-inflammatory and other biological activities, serving as an important precursor of high-value products such as hydroxytyrosol and salidroside. Therefore, the green and efficient biosynthesis of tyrosol and its derivatives has become a research hotspot in recent years. Building cell factories by metabolic engineering of microorganisms is a potential industrial production way, which has low costs and environmental friendliness. This paper introduces the biosynthesis pathway of tyrosol and presents the key regulated nodes in the de novo synthesis of tyrosol in Escherichia coli and Saccharomyces cerevisiae. In addition, this paper reviews the recent advances in metabolic engineering for the production of hydroxytyrosol and salidroside. This review can provide a reference for engineering the strains for the high-yield production of tyrosol and its derivatives.

The association between serum vitamin A concentrations and virus hepatitis among U.S. adults from the NHANES database: a cross-sectional study.

Objective: According to the present study, the relationship between vitamin A (VA) levels and hepatitis virus carriage has been unclear and controversial. This study aimed to determine the potential relationship between serum VA levels and viral hepatitis and to provide ideas for future clinical treatments. Methods: A cross-sectional study was performed using the 2005-2006 and 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets. Multiple linear regression and logistic regression were adopted to analyze the association between serological hepatitis B surface antigen (HBsAg) or hepatitis C RNA (HCV-RNA) positivity and VA levels. There were 5,351 HBsAg-related responders and 242 HCV-RNA-related responders, including 52 HBsAg (+) and 104 HCV-RNA (+) responders. Results: Compared with HBsAg (-) and HCV-RNA (-) respondents, HBsAg (+) and HCV-RNA (+) respondents tended to have lower serum VA levels, respectively [1.63 (1.33 ~ 2.01) vs. 1.92 (1.57 ~ 2.34), P < 0.001; 1.54 (1.25 ~ 1.83) vs. 1.78 (1.46 ~ 2.26), P < 0.001]. A greater percentage of responders in the subclinical VA deficiency (SVAD) group were HBsAg (+) and HCV-RNA (+) than were those in the normal VA (VAN) group [2.4% (9/374) vs. 0.9% (43/4977), p = 0.003; 61.5% (16/26) vs. 40.7% (88/215), p = 0.043]. According to the results of the multiple regression analyses of the different models, the serum VA concentration was negatively correlated with HBsAg (+) and HCV-RNA (+) status (ß = -0.14, 95% CI = -0.30 to -0.01, p = 0.066; ß = -0.29, 95% CI = -0.50 ~ -0.09, p = 0.005, respectively). Compared to those with SVAD, patients with VAN were less likely to be serologically HBsAg (+) or HCV-RNA (+) (OR = 0.53, 95% CI = 0.25 ~ 1.10, p = 0.089; OR = 0.39, 95% CI = 0.18 ~ 0.84, p = 0.016, respectively). Conclusion: Our study provides evidence that patients who are HBsAg (+) or HCV-RNA (+) have a high incidence of SVAD. Moreover, HBsAg and HCV-RNA positivity are negatively correlated with VA levels, and patients with SVAD are more likely to carry HBsAg (+) or HCV-RNA (+). These findings suggest that the relationship between hepatitis viruses and vitamin A needs to be validated by more basic studies and clinical large-sample randomized controlled trials to provide ideas for new therapeutic targets.

Inverse metabolic engineering based on metabonomics for efficient production of hydroxytyrosol by Saccharomyces cerevisiae.

Metabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.

[Impact of cecal ligation and puncture-induced sepsis on the proliferation and differentiation of intestinal stem cells].

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.

[Analysis of Risk Factors for Pulmonary Infection in Patients with Acute Leukemia after Chemotherapy].

OBJECTIVE: To investigate the risk factors of pulmonary infection in patients with acute leukemia (AL) after chemotherapy. METHODS: A total of 294 patients with AL were collected and divided into infection group (n=93) and control group (n=201) according to whether the pulmonary infection occurred after chemotherapy. Analyze the correlation between sociodemographic data (sex, age, BMI), clinical data (disease type, ECOG score, invasive procedure, underlying disease, hormone therapy, empirical use of antibiotics, prognosis stratification, chemotherapy intensity, primitive cell count, white blood cell count, neutrophil count, duration of granulocyte deficiency, platelet count, hemoglobin, and albumin and pulmonary infection after chemotherapy. COX regression method was used to analyze the risk factors of pulmonary infection in AL patients after chemotherapy. RESULTS: Among 294 patients with AL, 11 died within 30 days after pulmonary infection. There were statistically significant differences in age, smoking history, ECOG score, invasive procedure, hormone therapy, empirical use of antibiotics, prognosis stratification, chemotherapy intensity, primitive cell count, neutrophil count, duration of granulocyte deficiency, platelet count, hemoglobin, albumin and fasting blood glucose between the 2 groups (P <0.05). COX regression analysis showed that smoking history, invasive procedure, unexperienced use of antibiotics, poor prognosis, long duration of granulocytopenia, low platelet level and low albumin were high risk factors for pulmonary infection in AL patients after chemotherapy (P <0.05). CONCLUSION: Smoking, invasive procedures, unexperienced use of antibiotics, poor prognosis, long duration of granulodeficiency, low platelet levels and low albumin are risk factors for pulmonary infection in AL patients after chemotherapy.

[Research Progress of Bispecific Antibodies in Treatment of Multiple Myeloma--Review].

Multiple myeloma (MM) is an incurable malignant plasma cell diseases, the incidence of which is increasing year by year. The application of immunomodulators drugs, proteasome inhibitors, anti-CD38 antibodies, CAR-T, and HSCT have significantly improved the prognosis of patients with MM, however new therapeutic tools need to be developed to improve the prognosis of patients with relapsed/refractory after conventional regimens treatment. Bispecific antibodies are a novel immunotherapeutic approach that generates immune synapses by binding to targets on malignant plasma cells and cytotoxic immune effector cells (T cells/natural killer cells), leading to T/NK cells activation and malignant plasma cell lysis. Several preclinical and phase I clinical studies have shown good efficacy, bringing new possibilities for patients with relapsed/refractory MM to improve their prognosis in the future in combination with the rest of the treatment options. This article summarizes the classification of bispecific antibodies developed in recent years, and the results of preclinical and clinical trials, which will provide some reference for treating MM.

Rapid room-temperature phosphorescence chiral recognition of natural amino acids.

Chiral recognition of amino acids is very important in both chemical and life sciences. Although chiral recognition with luminescence has many advantages such as being inexpensive, it is usually slow and lacks generality as the recognition module relies on structural complementarity. Here, we show that one single molecular-solid sensor, L-phenylalanine derived benzamide, can manifest the structural difference between the natural, left-handed amino acid and its right-handed counterpart via the difference of room-temperature phosphorescence (RTP) irrespective of the specific chemical structure. To realize rapid and reliable sensing, the doped samples are obtained as nanocrystals from evaporation of the tetrahydrofuran solutions, which allows for efficient triplet-triplet energy transfer to the chiral analytes generated in situ from chiral amino acids. The results show that L-analytes induce strong RTP, whereas the unnatural D-analytes produce barely any afterglow. The method expands the scope of luminescence chiral sensing by lessening the requirement for specific molecular structures.

Water-Ice Microstructures and Hydration States of Acridinium Iodide Studied by Phosphorescence Spectroscopy.

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5 M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5 M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

Association between body mass index and delirium incidence in critically ill patients: a retrospective cohort study based on the MIMIC-IV Database.

OBJECTIVES: Delirium is a form of brain dysfunction with high incidence and is associated with many negative outcomes in the intensive care unit. However, few studies have been large enough to reliably examine the associations between body mass index (BMI) and delirium, especially in critically ill patients. The objective of this study was to investigate the association between BMI and delirium incidence in critically ill patients. DESIGN: A retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care-IV V2.0 Database consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. PARTICIPANTS: A total of 20 193 patients with BMI and delirium records were enrolled in this study and were divided into six groups. PRIMARY OUTCOME MEASURE: Delirium incidence. RESULTS: Generalised linear models and restricted cubic spline analysis were used to estimate the associations between BMI and delirium incidence. A total of 30.81% of the patients (6222 of 20 193) developed delirium in the total cohort. Compared with those in the healthy weight group, the patients in the different groups (underweight, overweight, obesity grade 1, obesity grade 2, obesity grade 3) had different relative risks (RRs): RR=1.10, 95% CI=1.02 to 1.19, p=0.011; RR=0.93, 95% CI=0.88 to 0.97, p=0.003; RR=0.88, 95% CI=0.83 to 0.94, p<0.001; RR=0.94, 95% CI=0.86 to 1.03, p=0.193; RR=1.14, 95% CI=1.03 to 1.25, p=0.010, respectively. For patients with or without adjustment variables, there was an obvious U-shaped relationship between BMI as a continuous variable and delirium incidence. CONCLUSION: BMI was associated with the incidence of delirium. Our results suggested that a BMI higher or lower than obesity grade 1 rather than the healthy weight in critically ill patients increases the risk of delirium incidence.

An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota.

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A's role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A's therapeutic potential in IM treatment and provides insights for future research.

Switching Electrocatalytic Hydrogen Evolution Pathways through Electronic Tuning of Copper Porphyrins.

The electronic structure of metal complexes plays key roles in determining their catalytic features. However, controlling electronic structures to regulate reaction mechanisms is of fundamental interest but has been rarely presented. Herein, we report electronic tuning of Cu porphyrins to switch pathways of the hydrogen evolution reaction (HER). Through controllable and regioselective ß-oxidation of Cu porphyrin 1, we synthesized analogues 2-4 with one or two ß-lactone groups in either a cis or trans configuration. Complexes 1-4 have the same Cu-N4 core site but different electronic structures. Although ß-oxidation led to large anodic shifts of reductions, 1-4 displayed similar HER activities in terms of close overpotentials. With electrochemical, chemical and theoretical results, we show that the catalytically active species switches from a CuI species for 1 to a Cu0 species for 4. This work is thus significant to present mechanism-controllable HER via electronic tuning of catalysts.

Quemeiteng granule relieves goiter by suppressing thyroid microvascular endothelial cell proliferation and angiogenesis via miR-217-5p-mediated targeting of FGF2-induced regulation of the ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Goiters are enlargements of the thyroid gland and are a global public issue. Quemeiteng granule (QMTG) is a traditional Chinese medicine (TCM) formula used to treat goiter in Yunnan Province. However, the effectiveness and underlying mechanism of these treatments have not been fully elucidated. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of QMTG on goiter and the downstream regulatory mechanisms. MATERIALS AND METHODS: In this study, we first evaluated the antigoiter efficacy of QMTG through biochemical indices [body weight, thyroid coefficient, triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)] and hematoxylin-eosin (HE) staining in a Propylthiouracil (PTU)-induced model. Based on microRNA sequencing (miRNA-seq) and bioinformatics analysis, key miRNA was screened out. A dual-luciferase reporter assay was performed to confirm the transcriptional regulation of the target gene by the miRNA. The viability of rat thyroid microvascular endothelial cells (RTMECs) and human thyroid microvascular endothelial cells (HTMECs) was assessed using the CCK-8 assays. The migration and angiogenesis of RTMECs and HTMECs were visualized through tube formation and wound scratch assays. Proteins involved in angiogenesis and the ERK pathway were assessed via Western blotting. RESULTS: QMTG significantly increased body weight, decreased the thyroid coefficient, increased the levels of T3, T4, FT3 and FT4 and reduced TSH levels in rats with goiter. QMTG also promoted the morphological recovery of thyroid follicles. MiR-217-5p was identified as a key miRNA. Our studies revealed that miR-217-5p directly targets FGF2 and that QMTG promotes the recovery of thyroid hormone (TH) levels and morphological changes in the thyroid, suppresses thyroid microvascular endothelial cell vitality, tube formation and migration, and reduces the expression of VEGF, Ang-1 and VCAM-1 triggered by miR-217-5p, thereby inhibiting the Ras/MEK/ERK cascade through FGF2. CONCLUSIONS: Our experiments demonstrated that the QMTG had therapeutic effects on goiter. These effects were attributed to the inhibition of ERK pathway-induced proliferation and angiogenesis through the targeting of FGF2 by miR-217-5p.

High Serum Albumin Levels were Associated with Acute Kidney Injury in Pediatric Surgical Intensive Care Units.

INTRODUCTION: There are limited studies revealing the association between serum albumin concentrations and acute kidney injury (AKI) in critically ill children. METHODS: This was a multicenter retrospective study. Children consecutively admitted to four pediatric surgical intensive care units (PSICUs) between January 2016 and December 2020 were screened for analysis. Patients without recorded albumin values during the PSICU stay were excluded. Data were extracted from the electronic medical records systems of the hospitals. AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The associations between serum albumin levels and AKI were assessed by using logistic regression models. RESULTS: A total of 7802 children were included in the analysis. The median age of the children was 1.0 (interquartile range (IQR), 0.0-4.0) years. There were 3214 (41.2 %) children who developed AKI. In the univariate logistic regression model, serum albumin levels were associated with AKI (odds ratio (OR) = 1.04, 95 % confidence interval (CI) 1.04-1.05). After adjusting for covariates, serum albumin showed an independent association with AKI (OR = 1.04, 95 % CI 1.03-1.05). Albumin levels above 39.43 g/L (OR = 1.036, 95 % CI 1.002-1.070) were associated with AKI in the unadjusted cubic spline. In the adjusted cubic spline, albumin levels above 40.41 g/L (OR = 1.061, 95 % CI 1.003-1.122) were associated with AKI. CONCLUSION: High serum albumin was associated with AKI in critically ill children in the PSICU. Further studies are needed to validate our findings. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: LEVEL II.

Efficacy and safety of patient-controlled epidural analgesia versus patient-controlled intravenous analgesia following open hepatectomy: A single-center retrospective study.

Background: Postoperative analgesia is an essential component of enhanced recovery after surgery following abdominal surgery. Studies comparing the effectiveness of epidural analgesia with that of other analgesic modalities after liver surgery have reported inconsistent results. Consequently, the use of epidural analgesia for open hepatectomy is controversial. Objective: The present single-center retrospective study aimed to compare the efficacy and safety of patient-controlled epidural analgesia (PCEA) and patient-controlled intravenous analgesia (PCIA) in adults undergoing open hepatectomy. Methods: Patients who underwent open hepatectomy between January 2018 to December 2019 at Zhongshan Hospital, Fudan University were retrospectively analyzed. Propensity score matching was used to adjust baseline information between the PCEA and PCIA groups. The primary outcome measure was scores of the numeric rating scales (NRSs) for resting, exercise, and nocturnal pain at postoperative 24 h (postoperative day 1 [POD1]) and 48 h (POD2). The secondary outcome indicators included postoperative nausea and vomiting (PONV), hypotension, pruritus, respiratory depression, functional activity score (FAS), effective analgesic pump compression ratio, analgesic relief rate, discontinuation of the analgesic pump, reasons for discontinuation of the analgesic pump, and patient satisfaction with postoperative analgesia. Results: The NRS scores of the PCEA group on POD1 were significantly lower than those of the PCIA group (P < 0.05). On POD2, the difference between the two groups was significant only for motion NRS scores (P < 0.05). The PCIA group had significantly more patients with lower FAS functional class than the PCEA group (P < 0.001). The effective analgesic pump compression ratio and the analgesic relief rate at 2 days after the surgery were lower in the PCEA group than in the PCIA group (P < 0.001). The incidence of pump discontinuation was higher in the PCEA group than in the PCIA group on POD2 (P = 0.044). Moreover, on POD1 and POD2, the PCEA group showed a higher incidence of pruritus and hypotension than the PCIA group (P < 0.001). Both groups showed no significant difference in PONV incidence. Conclusion: In patients undergoing open hepatectomy, PCEA was more effective than PCIA in relieving moderate to severe pain on POD1. However, improving the safety and effectiveness of PCEA remains a challenge.

2D-Graph of intermolecular interactions predicts radical character of anion-π* type charge-transfer complexes.

The molecular orbital (MO) theory is one of the most useful methods to describe the formation of a new chemical bond between two molecules. However, it is less often employed for modelling non-bonded intermolecular interactions because of the small charge-transfer contribution. Here we introduce two simple descriptors, the energy difference (EDA) of the HOMO of an electron donor and the LUMO of an acceptor against such HOMO-LUMO overlap integral (SDA), to show that the MO theory could give a unified charge-transfer picture of both bonding and non-bonding interactions for two molecules. It is found that similar types of interactions tend to be closer to each other in this 2D graph. Notably, in a transition region from strong bonding to single-electron transfer, the interacting molecular pairs appear to present a "hybrid" between chemical bonding and a radical pair, such as anion-π* interactions. It is concluded that the number of nodes in the HOMO and LUMO play a crucial role in determining the bonding character of the molecular pair.

An inulin-type fructan CP-A from Codonopsis pilosula alleviates TNBS-induced ulcerative colitis based on serum-untargeted metabolomics.

Ulcerative colitis (UC) is an inflammatory disease with abdominal pain, diarrhea, and bloody stool as the main symptoms. Several studies have confirmed that polysaccharides are effective against UC. It is commonly accepted that the traditional benefits of Radix Codonopsis can be attributed to its polysaccharide contents, and inulin-type fructan CP-A is the main active monomer in the polysaccharide components. Herein, we established a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) to investigate the effect of CP-A on UC. Untargeted metabolomics studies were conducted to identify differential metabolites using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and enrich metabolic pathways in rat serum. The in vivo assays demonstrated that CP-A reduces colonic macroscopic injury, disease activity index (DAI), histopathological score, interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) levels, as well as the expression of intercellular adhesion molecules. On the other hand, CP-A increases IL-10 and transforming growth factor-ß (TGF-ß) levels. The in vitro experiments indicated that CP-A treatment could reduce nitric oxide (NO) and IL-1ß after LPS stimulation. The metabolomics results suggested that CP-A therapy for UC may be related to the mammalian target of rapamycin (mTOR) signaling pathway. The in vitro and in vivo validation of the pathway showed similar results, indicating that CP-A alleviates UC by preventing the activation of mTOR/p70S6K signaling pathway. These findings offer a fresh approach to treating UC and a theoretical foundation for the future advancement of CP-A.NEW & NOTEWORTHY We report that an inulin-type fructan from Codonopsis pilosula CP-A exhibits a therapeutic effect on experimental colitis. Its mechanism may be to alleviate intestinal inflammation by preventing the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. These findings offer a fresh approach to treating ulcerative colitis (UC) and a theoretical foundation for the future advancement of CP-A.

Kaposiform Hemangioendothelioma with Bone Destruction: A 16-Year Follow-Up Cohort Study of the Clinical Characteristics and Prognosis.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment. METHODS: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction. RESULTS: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach-Merritt phenomenon (P = 0.006). CONCLUSIONS: Based on the rarity and significant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long-term complications of KHE with bone destruction and improve the quality of life of patients. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: Level II.

Laparoscopic Ladd's procedure for intestinal malrotation in small infants with midterm follow-up.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of laparoscopic Ladd's procedure (LL) for intestinal malrotation (IM) in small infants. METHODS: All patients aged < 6 months with IM who underwent Ladd's procedures between January 2012 and December 2019 were enrolled. The perioperative demographics and midterm follow-up results were retrospectively reviewed and compared between patients who underwent LL and open Ladd's operation (OL). RESULTS: Fifty-five patients were enrolled for analysis. The baseline characteristics were well matched in the two groups. The rate of volvulus was similar in the two groups (76.2% vs. 73.5%, P = 0.81). Two cases in the LL group were converted to OL due to intraoperative bleeding and intestinal swelling. The operative time (ORT) was not significantly different between the two groups (73.8 ± 18.7 vs. 66.8 ± 11.6 min, P = 0.76). Compared to the OL group, the LL group had a shorter time full feed (TFF) (3.1 ± 1.2 vs. 7.3 ± 1.9 days, P = 0.03) and a shorter postoperative hospital stay (PHS) than the OL group (5.5 ± 1.6 vs. 11.3 ± 2.7 days, P = 0.02). The rate of postoperative complications was similar in the two groups (9.5% vs. 11.8%, P = 0.47). The LL group had a lower rate of adhesive obstruction than the OL group, but the difference was not significant (0.0% vs. 11.8%, P = 0.09). One patient suffered recurrence in the LL group, while 0 patients suffered recurrence in the OL group (4.8% vs. 0.0%, P = 0.07). The rate of reoperation in the two groups was similar (4.8% vs. 8.8%). CONCLUSIONS: The LL procedure for IM in small infants was a safe and reliable method that had a satisfactory cosmetic appearance and shorter TFF and PHS than OL.

The association between procalcitonin and acute kidney injury in patients stung by wasps.

Introduction: The aim of this study was to investigate the status of serum procalcitonin (PCT) in patients stung by wasps and evaluate the association between PCT levels and acute kidney injury (AKI). Methods: Patients stung by wasps admitted to two tertiary hospitals between January 2017 and December 2020 were screened for enrollment. We evaluated serum PCT levels on admission in patients stung by wasps. The patients were divided into an AKI group and a non-AKI group. A logistic regression model was used to analyze the association between PCT status and AKI. The performance of PCT concentrations in predicting the occurrence of AKI was evaluated by the area under the receiver operating characteristic curve (AUROC). Results: A total of 138 patients were enrolled, and 66 patients suffered AKI. PCT levels were elevated in 78.99% of patients stung by wasps. Nearly half of the patients (47.83%) developed AKI. PCT levels were correlated with creatinine levels on admission (r = 0.787, 95% CI: 0.713-0.844). PCT levels in patients with AKI were higher than those in patients without AKI (p < 0.001). After adjustment for covariates, PCT levels on admission were independently associated with AKI (OR: 1.575, 95% CI: 1.071-2.317, p = 0.021). The AUROC of PCT levels on admission was 0.837 (95% CI, 0.771-0.902, p < 0.001). A PCT level of 0.57 µg/L was the cutoff for maximizing the Youden index; the specificity was 79.45%, and the sensitivity was 73.43%. Conclusion: Serum PCT levels may be a potential biomarker of AKI in patients stung by wasps.