Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

AIM To evaluate the habitat suitability of Hedysari Radix based on MaxEnt model and ArcGIS.METHODS Using the MaxEnt model to screen the ecological factors affecting the distribution of Hedysari Radix,an evaluation model was thus established.ArcGIS software was used to evaluate the ecological suitability of Hedysari Radix to obtain the data about the highly suitable area,the moderate suitable area,the low suitable area and non-suitable area for its growth in China.RESULTS Hedysari Radix found its 1.29×106 km2 suitable area in China,among which the highly suitable area was 5×104 km2,mainly in Gansu Province,the moderately suitable area was 3.38×105 km2,and the low-suitable area was 9×105 km2,occupying 4.03%,26.20%and 69.77%of all,respectively.The main ecological factors affecting the distribution of Hedysari Radix were determined to be altitude,precipitation in the hottest quarter,solar radiation in September and December,seasonal temperature variation deviation and basic saturation of upper soil(0-30 cm).CONCLUSION With its result complying well with the literature records,this study provides theoretical basis for the introduction and cultivation of Hedysari Radix,and sustainable utilization of resources as well.

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.
Anastomosis, Surgical/methods* ; Esophagogastric Junction/surgery* ; Gastrectomy/methods* ; Gastroesophageal Reflux/surgery* ; Humans ; Quality of Life ; Stomach Neoplasms/surgery*

Objective: Traditional Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy can greatly decrease the anastomosis-related complications and reduce the incidence of reflux esophagitis, but its complexity limits the wide application. To decrease the complexity of Kamikawa anastomosis, the surgical team of Changzhi People's Hospital of Shanxi Changzhi Medical College improved this technique by using novel notion and reduced surgical procedures. This study aims to evaluate the efficacy and safety of modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy. Methods: A descriptive cohort study was carried out. Case enrollment criteria: (1) upper gastric carcinoma or esophagogastric junction carcinoma without distant metastasis was confirmed by preoperative gastroscopic biopsy and imaging examination; (2) tumor diameter was less than 4 cm; (3) preoperative clinical staging was cT1-3N1M0. Exclusion criteria: (1) patients received preoperative neoadjuvant chemotherapy; (2) patients had severe heart or lung disease, or poor nutritional status so that they could not tolerate surgery. Clinical data of 25 patients with upper gastric carcinoma or esophagogastric junction carcinoma who underwent modified Kamikawa anastomosis in digestive tract reconstruction in Heji Hospital (8 cases) and Changzhi People's Hospital (17 cases) from April 2019 to December 2020 were retrospectively collected. Of 25 patients, 21 were male and 4 were female, with mean age of 63.0 (49 to 78) years; 3 underwent open surgery and 22 underwent laparoscopic surgery. The modified Kamikawa anastomosis was as follows: (1) the novel notion of total mesangial resection of the esophagogastric junction was applied to facilitate the thorough removal of lymph nodes and facilitate hand-sewn anastomosis and embedding; (2) the diameter of the anastomotic stoma was selected according to the diameter of the esophageal stump, between 2.5 and 3.5 cm, to reduce the occurrence of anastomotic stenosis; (3) an ultrasonic scalpel was used to incise the esophageal stump, which could not only prevent bleeding of the esophageal stump, but also closely seal the esophageal mucosa, muscle layer and serosa to prevent esophageal mucosa retraction; (4) barbed suture was used to suture the remnant stomach fundus and esophagus to fix the stomach fundus in order to reduce the cumbersome and difficult intermittent sutures in a small space; (5) two barbed sutures were used to continuously suture the front and back walls of the anastomosis and complete the suture and fixation of the muscle flap. Relevant indicators of surgical safety, postoperative complications (using the Clavien-Dindo classification), esophageal reflux symptoms and the occurrence of esophagitis (using Los Angeles classification) were analyzed. The gastroesophageal reflux disease (GERD) score, gastroscopy, multi-position digestive tract radiography during postoperative follow-up were used to evaluate the residual gastric motility and anti-reflux efficacy. Results: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy was successfully performed in 25 patients. The surgical time was (5.8±1.8) hours, the intraoperative blood loss was (89.2±11.8) ml, and the average hospital stay was (13.8±2.9) days. Three cases (12.0%) developed postoperative anastomotic stenosis as Clavien-Dindo grade III and were healed after endoscopic dilation treatment. Postoperative upper gastrointestinal radiography showed 1 case (4.0%) with reflux symptoms as Clavien-Dindo grade I. Gastroscopy showed no signs of reflux esophagitis, and its Los Angeles classification was A grade. No anastomotic bleeding, local infection and death were found in all the patients. At postoperative 6-month of follow-up, GERD score showed no significant difference compared to pre-operation (2.7±0.6 vs. 2.4±1.0, t=-1.495, P=0.148). Conclusion: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy is safe and feasible with good anti-reflux efficacy.
Aged ; Anastomosis, Surgical ; Cohort Studies ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Retrospective Studies

Background::Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods::In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells. Results::MCPIP1 was up-regulated by LA-MCPIP1 ( P < 0.001) and plasmid-MCPIP1 ( P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001). Conclusion::The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.

ObjectiveTo investigate the relationship between the levels of D-dimer and inflammatory factors C-reactive protein（CRP）and prognosis in patients with 2019 novel coronavirus-infected pneumonia（COVID-19）.Methods The clinical data of a total of 242 patients with COVID-19 who were treated in hospital from February 4th 2020 to February 18th 2020 were analyzed retrospectively. According to the classification standard,the patients with COVID-19 were divided into common patients(131 cases), severe patients（88 cases）, and critical patients（23 cases）. The difference between the levels of D-dimer and CRP in patients with pneumonia of different severity and clinical outcomes was compared and the correlation between D-dimer and CRP was analyzed.ResultsThe levels of D-dimer and CRP in severe and critical patients were significantly higher than those in common patients(P<0.05). The levels of CRP in critical patients were significantly higher than those in severe patients(P<0.05). These two indicator levels of patients who died of COVID-19 within 30 dayswere significantly higher than those who survived. Pearson correlation analysis showed that the levels of D-dimer were positively correlated with the levels of CRP(r=0.649，P<0.05).ConclusionD-dimer and CRP are highly expressed in severe and critical patients, and the severe abnormality of the two indicators in the early stage of COVID-19 predicted the poor prognosis. D-dimer and CRP have certain clinical value in evaluating the severity and prognosis of COVID-19.

Soil microorganisms are one of the important biological indictors of soil quality and can reflct the comprehensive ecological environment characteristics of the soil. The research of soil microbial diversity is the key to know the ecological functions and balance with soil. In this paper, high-throughput sequencing on PCR-amplified 16 S rRNA gene V3-V4 fragments was used to determine the bacterial diversity in rhizosphere soil of A. macrocephala under the treatment with BZJN1 or streptoprofen. The results showed that there were no significant differences of the bacteria in A. macrocephala rhizosphere soil of the streptoprofen treatment group and the biocontrol BZJN1 treatment group. All the soil bacteria was classified into 25 categories,67 classes, 108 orders, 167 families and 271 generas, except some unidentified bacteria. Proteobacteria(30.7%-34.8%) was the dominant phylum, of which Alphaproteobacteria(16.8%-18.5%) was the dominant subgroup. Compared with the control group, the relative abundance of multiple phylums bacteria in the rhizosphere soil of A. macrocephala was significantly changed in the streptoprofen treatment group and the biocontrol BZJN1 treatment group. In addition, RDA analysis showed that there was connection with different environmental factors and microbial communities. The abundance of the three genera in the rhizosphere soil of A. macrocephala was significantly positively correlated with Invertase, Urease and AP. PICRUSt function prediction results showed that BZNJ1 could enhance some bacterial functions and promote the plant growth. Biocontrol is a new type of green and safety control pest method. BZNJ1 significantly enhances some bacterial functions on the basis of effectively preventing root rot of A. macrocephala and promoting plant growth, and has no significant effect on the soil bacterial community structure. All the results can provide theoretical support for popularization of BZNJ1.
Atractylodes ; Bacteria ; Rhizosphere ; Soil ; Soil Microbiology

OBJECTIVE: To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA). METHODS: Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis. RESULTS: EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01). CONCLUSION EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)