Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

BACKGROUND:With the progress of minimally invasive procedures of the spine,endoscopic lumbar decompression has been widely used in the treatment of lumbar disc herniation.The indications of different endoscopic surgical approaches are different,and the decision of the specific operation plan needs to be combined with the actual situation and the choice of clinical surgeons. OBJECTIVE:To investigate the short-term effect in treatment of single-level lumbar disc herniation by percutaneous endoscopic visual trephine arthroplasty. METHODS:Ninety patients with single-level lumbar disc herniation admitted to Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2021 who met the inclusion criteria were included in this study.According to different approaches of percutaneous endoscopic visual trephine arthroplasty,they were divided into transforaminal approach group(control group,n=48 cases)and translaminar approach group(trial group,n=42 cases).The general information of patients in the two groups was recorded,including sex,age,disease course,body mass index,incision length,operation time,intraoperative fluoroscopy times,length of hospital stay,and amount of blood loss.Visual analog scale score of pain and Japanese Orthopaedic Association score at different follow-up stages were assessed.The modified MacNab standard was used to evaluate the clinical outcome at the last follow-up,and the postoperative complications and recurrence rate were measured. RESULTS AND CONCLUSION:(1)The operation time and intraoperative fluoroscopy times of the trial group were less than those of the control group,and the difference was statistically significant(P<0.05).However,there were no significant differences in intraoperative blood loss,incision length,and hospital stay between the two groups(P>0.05).(2)There was no significant difference in visual analog scale score of pain and Japanese Orthopaedic Association score between the two groups before surgery(P>0.05).However,visual analog scale of pain and Japanese Orthopaedic Association score were significantly improved 1 week,3,6,and 12 months after surgery(P<0.05).(3)At the last follow-up,the good and good rate of modified MacNab standard was 94%in the control group and 95%in the trial group.(4)In the control group,one patient still felt back and leg pain after surgery,underwent open surgery,and recovered well after surgery without obvious sequelae.There were no postoperative complications or recurrent cases in the trial group.(5)It is concluded that both percutaneous transforaminal approach and interlaminar approach have good short-term clinical efficacy and high patient satisfaction in the treatment of single-level lumbar disc herniation,but the time of the interlaminar approach is shorter and has less intraoperative fluoroscopy times.

Mitral valve replacement is one of the most common heart valve surgeries in China. In recent years, with the increase in degenerative valve diseases, older patients, and the progress of anti-calcification technology of biological valves, the proportion of mitral valve biological valve replacement has been increasing year by year. After the damage of traditional mitral valve biological valves, re-operation of valve replacement with thoracotomy is required. However, the adhesion between the heart and sternum, as well as the damage caused by cardiopulmonary bypass and cardiac arrest, can cause significant trauma to elderly patients and those with multiple organ dysfunction, leading to increased mortality and complication rates. In recent years, interventional valve surgery, especially transcatheter valve-in-valve surgery, has developed rapidly. This procedure can correct the damaged mitral valve function without stopping the heart, but there are still many differences between its technical process and conventional aortic valve replacement surgery. Therefore, organizing and writing multicenter expert recommendations on the technical process of transcatheter valve-in-valve surgery for damaged mitral valve biological valves is of great significance for the training and promotion of this technology.

Objective:To investigate the pathogenic spectrum of children with severe infection by metagenomic next generation sequencing (mNGS).Methods:This study was a cross-sectional study. We collected 212 cases of severely infected pediatric patients admitted to the Intensive Care Unit (ICU) of the Women and Children′s Hospital of Ningbo University from January 2022 to June 2023, and performed metagenomic next-generation sequencing (mNGS) on 249 samples to analyze the pathogenic distribution characteristics.Results:Among the 249 samples of 212 children, the positive detection rate was 49.80% (124/249), including 14 cases of mixed infections, accounting for 6.60% (14/212). According to the mNGS technology, the pathogen distribution of severely infected children showed that the most common Gram-positive bacteria were Staphylococcus aureus (3.61%, 9/249), Streptococcus pneumoniae (2.81%, 7/249), and Staphylococcus epidermidis (2.41%, 6/249); the most common Gram-negative bacteria were Klebsiella aerogenes (2.41%, 6/249), Klebsiella pneumoniae (2.41%, 6/249), and Haemophilus parainfluenzae (2.01%, 5/249). The most common fungus was Candida parapsilosis (2.01%, 5/249). The most common virus was Human Cytomegalovirus (HCMV) (6.02%, 15/249), Human Herpesvirus 1 (HHV-1) (1.61%, 4/249), and Epstein-Barr virus (EBV) (1.61%, 4/249). The most common atypical pathogen was Mycoplasma pneumoniae (3.21%, 8/249). Conclusions:This study explored the pathogen spectrum in severely infected pediatric patients through mNGS, contributing to the diagnosis of mixed infections or infections caused by uncommon or rare pathogens, which enables rapid and efficient identification of pathogens.

Objective:To study the genotyping of thalassemia in Ningbo population and provide a reference basis for future prevention and control of thalassemia in Ningbo.Methods:Patients with suspected thalassemia attending Ningbo Women and Children's Hospital from January 2019 to March 2022 were selected for the study, and DNA was extracted from dried blood spot specimens by collecting peripheral blood, and detection of thalassemia hotspot variants was performed by fluorescence PCR melting curve analysis combined with Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).Results:A total of 2 680 cases were included in the patients with suspected thalassemia, and 1 426 cases of thalassemia gene carriers were detected, with an overall detection rate of 53.2%. Among them, 595 cases (41.7%) were α-thalassemia, with -- SEA/αα, αα/-α 3.7 and -- SEA/-α 3.7 being more common; 807 cases (56.6%) were β-thalassemia, with β IVS-Ⅱ-654/β N, β CD41-42/β N and β CD17/β N being more common; 24 cases (1.7%) were αβ-combined thalassemia. Among them, six rare variant types were included, including fusion gene (Fusion), -- FIL, HBA2:c.376C>T, CD8/9(+G), IVS-Ⅰ-2(T>C) and IVS-Ⅱ-1(G>A), all of which were reported for the first time in Ningbo. Conclusion:Among suspected thalassemia patients in Ningbo, the detection rate of thalassemia is high, and the types of gene variants are complex, so the awareness of thalassemia gene testing for anemic patients should be raised.

Objective:To study the results of thalassemia gene detection and prenatal diagnosis in pregnant women in Ningbo City, and analyze the characteristics of erythrocyte parameters in early pregnancy.Methods:A total of 636 suspected thalassemia pregnant women treated in Ningbo Women and Children's Hospital from January 2019 to September 2021 were selected as the research subjects, the dry blood spots of pregnant women were collected for thalassemia gene detection; and the amniotic fluid of pregnant women with thalassemia gene carried by both husband and wife was extracted for prenatal diagnosis, and the results of thalassemia gene detection and prenatal diagnosis were analyzed. Meanwhile, in the medical record system of Ningbo Women and Children's Hospital, the detection results of erythrocyte parameters in early pregnancy of pregnant women with thalassemia gene (thalassemia group) and healthy pregnant women (control group) were investigated. Erythrocyte parameters including hemoglobin (Hb), red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin content (MCH), mean corpuscular volume (MCV), hematocrit (HCT) and red blood cell distribution width (RDW) were compared between groups and among different thalassemia gene variants.Results:Among 636 suspected thalassemia pregnant woman, 254 cases (39.94%) were confirmed thalassemia gene carriers, including 114 cases of α-thalassemia, 132 cases of β-thalassemia, and 8 cases of αβ-compound thalassemia. After genetic counseling, 11 women finally received prenatal diagnosis, 7 fetuses (7/11) were found to carry thalassemia gene, including two cases of -- SEA/αα and β CD17/β N, respectively; one case of β CD26/β N, αα/-α 3.7 and β CD41-42/β CD41-42, respectively. The results of erythrocyte parameters detection showed that compared with the control group ( n = 80), there were statistically significant differences ( P < 0.05) in various erythrocyte parameters in α-thalassemia group ( n = 77) and β-thalassemia group ( n = 87); and there were significant differences ( P < 0.05) in Hb, HCT, MCV, MCH and MCHC among the four major genotypes (-- SEA/αα, β IVS-Ⅱ-654/β N, β CD17/β N and β CD41-42/β N). Conclusions:The genetic testing of thalassemia in pregnant women in Ningbo City is mainly α-thalassemia or β-thalassemia, and prenatal diagnosis is necessary for pregnant women carrying thalassemia gene. The erythrocyte parameters in early pregnancy of pregnant women carrying thalassemia gene are changed, and there are differences among different genotypes.

Objective    To investigate the early clinical results of MitraClip system in domestic patients. Methods     We retrospectively analyzed the clinical data of 36 patients who underwent transcatheter edge-to-edge repair procedure using MitraClip system in Beijing Fuwai Hospital, Shenzhen Fuwai Hospital and Fuwai Yunnan Cardiovascular Hospital between January and June 2021. There were 24 males and 12 females, with a median age of 70 (47-86) years. Ten (27.8%) patients had 3+ mitral regurgitation (MR) and 26 (72.2%) patients had 4+ MR preoperatively. Results    All procedures were successfully performed. The reduction in MR was 2+ at least immediately after surgery, and 91.7% of patients had MR≤2+ at 3 days postoperatively. There was no statistical difference in left ventricular ejection fraction change postoperatively. Forward velocity and peak gradient of mitral valve were increased after the procedure. Mean gradient of mitral valve were increased at 3 days postoperatively than immediately after surgery (P<0.001). Two patients had acute pericardial effusion intraoperatively, and received pericardial puncture and drainage immediately. Conclusion    MitraClip system has been applied well in domestic patients and can significantly improve MR. This sutdy has a good consistency with foreign studies, and the early results are satisfactory.