BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Objective To analyze the detection of helicobacter pylori(Hp)in different parts of gastric antrum,and to provide clinical guidance for finding the best biopsy site for Hp.Methods Patients who underwent 13C urea breath test and electronic gastroscopy from January 2020 to December 2022 were retrospectively analyzed and divided into 13C urea breath test positive group[delta over baseline(DOB)≥4]and 13C urea breath test negative group(DOB<4)according to DOB value.Gastroscopy reports and pathological data of patients were collected.According to different biopsy sites in gastric antrum,patients were divided into conventional biopsy site group,elevated erosive site group and flat erosive site group,and the detection rate of Hp in different biopsy sites was compared.13C urea breath test positive group was divided into group A(435)according to DOB value,and the gastric antral biopsy and pathology of each group were classified and analyzed.Combined with endoscopic reports and pathological data,patients were divided into atrophic gastritis group and non-atrophic gastritis group.Results In the 13C urea breath test positive group,the detection rate of Hp in the elevated erosive site group(96.4%)was higher than that in the conventional biopsy site group(92.7%)and the flat erosive site group(93.9%),and the difference was statistically significant(P = 0.036).In DOB group A,the detection rate of Hp was the highest at the site of elevated erosive and the lowest at the site of conventional biopsy,and the detection rate of Hp at the three biopsy sites was compared,the difference was statistically significant(P = 0.016);There was no significant difference in the detection rate of Hp at three biopsy sites between group B and group C(P = 0.622;P = 0.721);the non-atrophic gastritis group,the detection rate of Hp at the elevated erosive site(96.5%)was higher than that at the conventional biopsy site(91.2%)and the flat erosive site(92.0%),and the difference was statistically significant(P = 0.043).There was no significant difference in the detection rate of Hp at three biopsy sites in the atrophic gastritis group(P = 0.614).13C urea breath test negative group:There was no significant difference in Hp detection rate among the three biopsy sites(P = 0.255).Conclusion For patients with positive 13C urea breath test but low DOB value,the positive rate of Hp in the elevated erosive site is higher.For non-atrophic gastritis patients,the detection rate of Hp was higher in the elevated erosive sites than in the conventional biopsy sites.But for patients with atrophic gastritis,there was little difference in the detection rate of Hp in different parts of antrum.For patients with negative 13C urea breath test,there was no significant difference in Hp detection rate among the three biopsy sites.In future clinical work,for similar patients,precise biopsy can be performed to improve the detection rate of Hp.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective:To explore an assay that can concisely, rapidly, and accurately quantify the amount of chimeric antigen receptor (CAR)-T cells in the bone marrow or peripheral blood of patients after CAR-T cell immunotherapy by morphological analysis and flow cytometry assay, providing timely and accurate feedback for clinical treatment.Methods:We analyzed the CAR-T cell detection results in peripheral blood and bone marrow of 256 patients who received CAR-T cell immunotherapy in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University from August 2016 to August 2021. All 256 patients survived more than one month after CAR-T cell infusion. Among them, there were 118 patients with multiple myeloma, 68 patients with acute lymphoblastic leukemia, and 70 patients with lymphoma. The morphological characteristics, positive rate and detection rate of CAR-T cell in peripheral blood and bone marrow were analyzed by morphological methods. The positive rate and detection rate of CAR-T in peripheral blood and bone marrow were analyzed by flow cytometry protein L detection. χ 2 test was used to comprehensively analyze the difference between the detection rate of the combined analysis of the two methods and the detection rate of the single method. Results:CAR-T cells have significant morphological characteristics, and there are obvious morphological differences from normal lymphocytes. The detection rates of CAR-T cells in peripheral blood or bone marrow by morphological methods and flow cytometry were 88.28%(226/256) and 79.29% (203/256), respectively. When the two methods were combined, the detection rate of CAR-T cells can reach 99.22%, with statistically significant difference comparing to that of single method( P<0.05). Through the analysis of the detection results of peripheral blood at different time points, it was found that the average detection rates of morphology and flow cytometry in 118 patients with multiple myeloma were 9.50% and 10.23% on the 7th day, and 13.50% and 15.19% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 8.00% and 10.07%, respectively. The average detection rates of morphology and flow cytometry in 68 patients with acute lymphoblastic leukemia were 12.00% and 11.22% on the 7th day, and 21.00% and 23.10% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 13.50% and 10.91%, respectively. The average detection rates of morphology and flow cytometry in 70 lymphoma patients were 7.50% and 10.35% on the 7th day, and 9.00% and 10.35% respectively on the 15th day. The average detection rates of morphology and flow cytometry at 21 days were 6.50% and 5.69%, respectively. The number of CAR-T cells in samples from patients with different diseases reached a peak around the 15th day. Conclusion:The detection rate of CAR-T cells from peripheral blood or bone marrow was significantly higher with the combination of the 2 methods compared to the single method.

Objective:To investigate effects of bone-resorptive lesion on stress distribution of femoral head and on progression in patients with osteonecrosis of the femoral head (ONFH).Methods:From April 2014 to September 2018, a total of 155 femoral heads from 94 patients diagnosed with ARCO stage II and III ONFH were retrospectively reviewed, including 77 males and 17 females with aged 39.90±10.45 years old (ranged from 18-64 years). The hips were divided into two groups according to whether there were bone-resorptive lesions. Further, we compared whether there was statistical difference between the two groups in staging. Then, a case of ARCO II hip joint without bone-resorptive lesion was selected from the included patients. Six femoral head with different diameters of spherical bone-resorptive lesion of 5 mm, 7 mm, 10 mm, 14 mm, 18 mm, and 23 mm were simulated. The influence of bone-resorptive lesion on the stress distribution of necrotic area and a spherical shell extending 1 mm radially around the bone-resorptive lesion was investigated by finite element method in slow walking conditions.Results:Of the 155 ONFH hips, 67 hips are complicated by bone-resorptive lesions, of which 17 were ARCO II, 50 were ARCO III. A total of 88 hips did not contain bone-resorptive lesions, of which 58 were ARCO II, ARCO III 30 cases. The proportion of ARCO stage II in the group with bone-resorptive lesions was significantly higher than that in the group without bone-resorptive lesions (χ 2=25.03, P=0.000). The finite element stress distribution cloud diagram showed that there was a stress concentration area around the bone-resorptive lesions. The maximum von Mises stress around bone-resorptive lesions in the models that contained a synthetic bone-resorptive lesions were significantly higher than those reported in the matched, non-synthetic bone-resorptive lesions finite element models ( t=3.139, P=0.026). The values for maximum von Mises stress around bone-resorptive lesions were 6.94±1.78 MPa and 5.01±0.35 MPa for the group with synthetic bone-resorptive lesions and the group non-synthetic bone-resorptive lesions, respectively. There was a positive correlation between the diameter of bone-resorptive lesions and the maximum and mean von Mises stress of necrotic areas as well as the maximum von Mises stress around bone-resorptive lesions. Conclusion:Bone-resorptive lesions can increase the maximum stress and average stress in the necrotic area. The larger the bone-resorptive lesion, the more the stress increases. There is a stress concentration area around the bone-resorptive lesions, which may accelerate the collapse of the femoral head.

Objective:To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC).Methods:HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 μg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis.Results:CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 μg/ml groups was not significantly changed (all P>0.05), while that in the 200 μg/ml group was decreased ( P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 μg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 μg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 μg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 μg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 μg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion:Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.

Objective:To review the efficacy and safety in children receiving intranasal dexmedetomidine premedication before CT or magnetic resonance imaging (MRI).Methods:A literature search (search terms included "dexmedetomidine" "intranasal drug administration" "children" "CT" and "MRI") was conducted using Embase, PubMed, the Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, VIP database and Chinese Biomedical Literature Database (searched from inception to March 18, 2019). Randomized controlled trials of children receiving intranasal dexmedetomidine versus chloral hydrate, ketamine or midazolam premedication before CT or MRI were included. The Cochrane Reviewers′ Handbook 5.1.0 was used to evaluate the quality of the enrolled studies. The primary outcomes were sedation success rate and sedation induction time. The secondary outcomes included respiratory depression, heart rate, systolic blood pressure and blood oxygen saturation. Statistical analyses were performed using the Review Manager 5.3 software.Results:A total of 1 167 participants in 9 randomized controlled trials were included. The results of meta-analysis showed that intranasal dexmedetomidine premedication provided higher sedation success rate than oral chloral hydrate (relative risk ( RR) =1.13, 95% confidence interval ( CI) 1.02 to 1.26, P=0.020). There was no significant difference between intranasal dexmedetomidine and midazolam. In addition, the sedation induction time of intranasal dexmedetomidine group was significantly shorter than that in the oral chloral hydrate group (weighted mean difference -1.49, 95% CI -2.87 to -0.11; P=0.030), but showed no significant difference as compared with that of intranasal ketamine or midazolam. The patients treated with intranasal dexmedetomidine also showed significantly lower heart rate ( RR=4.78, 95 %CI 1.85-12.35, P=0.001) and less respiratory depression ( RR=0.28, 95 %CI 0.09-0.87, P=0.030). There were no intergroup differences in systolic blood pressure and blood oxygen saturation. Conclusions:Intranasal dexmedetomidine provided more effective sedation and higher safety in children undergoing CT or MRI. As this meta-analysis is limited by the small sample size, further high-quality randomized controlled trials are needed.

Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection.Methods CNKI, Wanfang database , PubMed, Embase and Cochrane library were systematically searched.Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled.The Cochrane Reviewers′Handbook 5.2 was employed to evaluate the quality of the enrolled studies. The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software.Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]＝1.07, 95%CI:0.93-1.24, P＞0.05), infection-related mortality rate (RR＝1.35, 95%CI:0.98-1.87, P＞0.05), bacterial clearance rate (RR＝0.85, 95%CI:0.71-1.02, P＝0.08), hepatotoxicity development rate (RR＝0.68, 95%CI:0.41-1.13, P＝0.14), and nephrotoxicity development rate (RR＝1.01, 95%CI:0.85-1.22, P＞0.05) between colistin monotherapy and combination therapy.The clinical response rate was higher in combination therapy than that in colistin monotherapy ( RR ＝0.81, 95%CI:0.66 -0.98, P ＝0.03).In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR＝1.00, 95%CI:0.86-1.12, P＞0.05). The dosage of colistin with or without loading dose was not associated with the treatment response .Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem -resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future.

Objective To study the effect of using different tibial nerve proximal muscle branchs to repair deep peroneal nerve injury in animal experiment, and to screen out the most optimal donor nerve branch. Methods From June, 2016 to August, 2016, 64 adult female SD rats were randomly divided into 4 groups, which were LHG (using lateral head of gastrocnemius to repair peroneal nerve), MHG(using medial head of gastrocnemius to repair peroneal nerve), SNB (using soleus nerve branch to repair peroneal nerve), and blank. There were16 rats in each group. At 4 and 8 weeks after surgery, each group were tested on behavior, electrophysiology, muscle tension, muscle wet weight and histology, to evaluate function recovery of the muscles controlled by deep peroneal nerve in each group, and to compare recovery of the deep peroneal nerve repaired by different tibial nerve branches. Results Eight weeks after surgery,right foot of the rats in LHG,MHG and SNB group can be extended,toes can be completely opened. Rats in blank group showed limping gait, whose right foot can not be extended, right toe can not be opened, and muscle atrophied. At 4 and 8 weeks after the operation, the recovery rate of LHG, MHG, SNB group (at 4th weeks, 33.60 ±2.22)%, 33.07 ±2.38% and 35.91 ±2.02%; at 8th weeks, 67.16 ±5.74)%, 66.56 ±3.18% and 73.17 ± 5.33%, respectively)was higher than blank group(7.71±1.05% and 7.84±0.78%, respectively)on CMAP amplitude, tibialis anterior muscle contractility, tibialis anterior muscle cell area, muscle cell area. SNB group was superior to the LHG group and LHG group.And the difference was statistically significant(P<0.05). Conclusion All the proxi-mal tibial nerve muscle branchs can be used to repair the deep peroneal nerve injury, and the soleus nerve branch is the preferred donor nerve.