CriteriaMapper: establishing the automatic identification of clinical trial cohorts from electronic health records by matching normalized eligibility criteria and patient clinical characteristics.

The use of electronic health records (EHRs) holds the potential to enhance clinical trial activities. However, the identification of eligible patients within EHRs presents considerable challenges. We aimed to develop a CriteriaMapper system for phenotyping eligibility criteria, enabling the identification of patients from EHRs with clinical characteristics that match those criteria. We utilized clinical trial eligibility criteria and patient EHRs from the Mount Sinai Database. The CriteriaMapper system was developed to normalize the criteria using national standard terminologies and in-house databases, facilitating computability and queryability to bridge clinical trial criteria and EHRs. The system employed rule-based pattern recognition and manual annotation. Our system normalized 367 out of 640 unique eligibility criteria attributes, covering various medical conditions including non-small cell lung cancer, small cell lung cancer, prostate cancer, breast cancer, multiple myeloma, ulcerative colitis, Crohn's disease, non-alcoholic steatohepatitis, and sickle cell anemia. About 174 criteria were encoded with standard terminologies and 193 were normalized using the in-house reference tables. The agreement between automated and manual normalization was high (Cohen's Kappa = 0.82), and patient matching demonstrated a 0.94 F1 score. Our system has proven effective on EHRs from multiple institutions, showing broad applicability and promising improved clinical trial processes, leading to better patient selection, and enhanced clinical research outcomes.

[Analysis of the efficacy of vocal cord botulinum toxin injection for refractory laryngeal contact granuloma].

Objective: To observe the efficacy of vocal cord botulinum toxin type A injection in the treatment of refractory laryngeal contact granuloma and to analyze the factors affecting the curative effect. Methods: Fifty-two patients with refractory laryngeal contact granuloma who received vocal cord botulinum toxin type A injection under topical anesthesia from May 2021 to May 2023 were analyzed retrospectively. Among them, 51 were males and 1 was female, aged 22-66 (48.98±8.87)years old. All patients were followed up for a minimum of 12 months. Outcome measures in terms of patient cure rate, total effective rate, complications and recurrence rate were calculated. The median [M (Q1, Q3)] was used to represent non-normally distributed measurement data, and Logistic regression analysis was used to determine independent risk factors affecting efficacy. Results: The cure rate of 52 patients with refractory laryngeal contact granuloma treated by vocal cord botulinum toxin type A injection was 78.8% (41/52), and the total effective rate (including cure, marked and effective) was 90.4% (47/52). The median number of injections was 1[1,2]. Following a single injection, the cure rate was 69.2% (36/52), and the median treatment duration for cured patients was 3 [3,3] months. Hoarseness occurred in 88.5% (46/52) of patients, with recovery within 3 months in all cases. Additionally, 21.2% (11/52) of the patients experienced cough, sore throat, dyspnea, all of whom recovered within 3 months. One patient among the 41 cured cases was lost to follow-up, and the recurrence rate at the 12th month was 17.5% (7/40). Multivariate regression analysis indicated that age, granuloma size, history of PPI treatment, previous corticosteroid injections, prior surgical excision, pharyngeal reflux, chronic cough, pharyngeal reflux, chronic cough and vocal overuse were not independent risk factors for cure and recurrence. Conclusion: Vocal cord botulinum toxin type A injection is an alternative for the treatment of refractory laryngeal contact granuloma, which offers benefits such ashigh cure rate, short treatment cycle and less injection times.

Tissue oxidative stress and expression of chicken UCP and ANT mRNA in laying hens exposed to acute cold stress.

1. Exposure to stress alters normal homoeostasis and, hence, the antioxidant defence system. The aim of this study was to examine the effect of acute cold temperature on the antioxidant defence system in hens.2. Hy-line grey commercial layers (80 40-week-old) were randomly assigned to one of eight groups. In groups 1 to 5, hens were exposed to low temperature at -8.68°C (cool stressed) for 2, 4, 6, 8 and 10 h, respectively. In groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C to recovery for 2 h and 4h, respectively. In treatment groups 6 and 7, post 10 h cool stressed, hens were quickly transferred to room at 21°C for 2 h and 4 h, respectively. Group 8 was the control, where hens were housed under regular condition at 21°C as controls.3. Antioxidant enzymes (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA), in skeletal muscle, the kidney, liver and pancreas were measured. The transcription of avUCP and ANT mRNA was tested by RT-PCR.4. The T-AOC activity was increased in the skeletal muscle of hens cold stressed for 2, 4, 6, 8 and 10 h and the 2 h recovery groups compared with control hens (p < 0.05). The GPx activity was increased in the liver and skeletal muscle after cold stress 4 h and in the pancreas of cold stress 2 h compared with the control group (p < 0.05). Antioxidant SOD activity was increased in the kidney after cold stress 6 h and in the liver after cold stress 10 h compared to the control group (p < 0.05). Measured MDA activity was increased in the pancreas after 2 h cold stress (p < 0.05).5. UCP mRNA expression level was increased in the pectoral muscle for 2 h and 4 h recovery groups compared with the control hens (p < 0.05) and avian uncoupling protein (UPC), adenine nucleotide translocator (ANT) expression level was increased in the leg muscle of hens cold stress for 2, 6, 8 h and recovery 2 and 4 h.6. The observed changes in the antioxidant defence system were tissue specific. Increments in levels of ANT (leg muscle) and UCP (pectoral and leg muscle) mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

[Clinical characteristics of 29 cases of pulmonary mucormycosis treated with and without surgery].

Objective: To analyze the clinical characteristics of patients with pulmonary mucormycosis treated with and without surgery. Methods: This was a single-center, retrospective study. We retrieved "pulmonary mucormycosis" from the electronic medical records of China-Japan Friendship Hospital between 2016 and 2022. A total of 29 patients with pulmonary mucormycosis were collected. There were 19 males and 10 females with a median age of 49 (47, 67) years. Mann-Whitney U test, χ² test, Kaplan-Meier curve and log-rank test were used to compare the differences between groups. Results: The most common underlying disease was diabetes (19, 65.5%). The most frequent imaging findings were consolidation (25, 86.2%) and nodule or mass (21, 72.4%). Bronchial stenosis (16, 55.2%), obstruction by fungal plugs (18, 62.1%), pseudomembranous necrotizing bronchitis (19, 65.5%) were common. Treatment strategies were developed by the multi-disciplinary team (MDT). Among 16 patients who did not undergo surgery, 10 had bilateral multifocal lesions and 6 had unifocal lesions. All patients received antifungal therapies, and surgeries were performed in 13 (44.8%) patients. Patients who underwent surgery had numerically lower in-hospital mortality (15.4% vs. 31.3%, P=0.410). Involvement of unilateral multiple lesions was more common in patients who underwent surgeries (6/13 vs. 1/16, P=0.019). Patients who underwent surgery were more likely to have lobar and segmental bronchial involvement (13/13 vs. 9/16, P=0.007). A total of 15 patients underwent mNGS, 14 (93.3%) had positive results. Performing metagenomic next generation sequencing for diagnosis shortened the time from disease onset to diagnosis (log-rank P=0.014). Conclusion: Metagenomic next-generation sequencing aided early diagnosis. The patients who underwent surgery included unilateral multiple lesions and visualisation of endobronchial abnormalities on lobar or segmental bronchus in unilateral lung.

[Mechanism of protective effect of metformin against septic cardiomyopathy based on the P38 MAPK/JNK signaling pathway].

Exploring the protective mechanism of metformin against septic cardiomyopathy based on the mitogen-activated protein kinase P38 (P38 MAPK)/c-Jun amino-terminal kinase (JNK) signaling pathway. This paper is an experimental animal study design, which was completed from January to December 2023 at the Xiangya Hospital, Central South University. Forty-eight 8-week-old female C57BL/6 mice were divided into four groups: group A (control group), group B (model group), group C (model+trimetazidine hydrochloride), and group D (model+metformin group), with 12 mice in each group, by using a randomized numeric table method. Groups B, C, and D were injected intraperitoneally with LPS (15 mg/kg) to construct a septic cardiomyopathy mouse model. 24 h after modeling, Groups A and B were injected intraperitoneally with an equal amount of saline, Group C was given 20 mg/kg trimetazidine hydrochloride by gavage, and Group D was injected with metformin 200 mg/kg intraperitoneally, and all of them were subjected to consecutive interventions for 14 d. The results were summarized in the following table. Ultrasound imaging system was used to detect cardiac function, and TUNEL method was used to detect apoptosis rate of myocardial tissues; real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of mRNA of JNK, P38 MAPK of P38 MAPK signaling pathway in the myocardial tissues of mice; Plasma creatine kinase isoenzyme (CK-MB), brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA) in all groups of mice; and protein kinase C, and protein kinase C levels were measured by protein blotting in cardiac muscle tissue. Eplison isoform (PKCε), and Cavity protein-3 (Cav-3) protein expression in myocardial tissues. The results showed that compared with group A, left ventricular ejection fraction (LVEF) (79.51±6.62)%, left ventricular short-axis shortening (FS) (45.66±4.13), apoptosis rate (4.34±0.36)%, JNK (0.96±0.06), P38 MAPK (1.01±0.03), CK-MB (2.37±0.13) µg/L, BNP (21.36±3.47) ng/L, TNF-α (176.22±19.24) ng/L, IL-6 (35.43±3.84) ng/L, PKCε expression (1.98±0.26), Cav-3 expression (1.04±0.03) compared to apoptosis rates in groups B, C, and D (28.22±4.49, 22.45±3.69, 15.88±3.27), JNK (1.68±0.11, 1.32±0.18, 1.13±0.14), P38 MAPK (2.47±0.71,1.77±0.35,1.49±0.05), CK-MB (16.55±2.16, 12.63±1.98, 5.27±0.61), BNP (48.92±5.67, 33.78±4.11, 27.55±3.84), TNF-α (463.71±24.81, 335.71±36.71, 214.78±22.53), and IL-6 (78.57±6.36, 63.71±5.66, 52.47±5.47) expression were elevated, while left ventricular ejection fraction (LVEF) (49.38±5.27, 55.47±5.03, 62.26±5.14), left ventricular short-axis shortening (FS) (24.36±2.17, 30.43±3.29, 33.57±2.72), PKCε expression (1.33±0.21, 1.54±0.23, 1.75±0.22), and Cav-3 expression (0.47±0.06, 0.76±0.05, 0.85±0.04) were all down-regulated (F=113.020,67.657,219.539,206.222,227.977,88.455,6285.186,135.877,65.924,96.362,17.532,314.419,P<0.05). Compared with group B, apoptosis rate, JNK, P38 MAPK, CK-MB, BNP, TNF-α, and IL-6 expression were decreased, and LVEF, FS, PKCε, and Cav-3 expression were up-regulated in groups C and D. And group D was better than group C (P<0.05). In conclusion, metformin has a protective effect against septic cardiomyopathy, and the mechanism may be related to the inhibition of the activation of the P38 MAPK/JNK signaling pathway and the up-regulation of PKCε and Cav-3 expression.

[Research progress of radiomics in hepatocellular carcinoma].

Primary liver cancer is a common malignant digestive system tumor, with hepatocellular carcinoma being the most common pathological type. Radiomics significantly boosts the efficiency of predictions by accurately capturing the intrinsically heterogeneous features of tumors that are difficult to discern with the human eye in imaging images. This article outlines the background and concepts of radiomics, introduces its latest research progress in various aspects, such as diagnosis and differential diagnosis, prediction of pathological molecular subtypes, efficacy evaluation, and survival prediction, and further discusses its limitations and prospects in HCC.

Erratum to 'Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress' [Research and Practice in Thrombosis and Haemostasis Volume 8, Issue 4, May 2024, 102432].

[This corrects the article DOI: 10.1016/j.rpth.2024.102432.].

[New intraoral digital impression with pneumatic gingival retraction used in the restoration of crown for posterior teeth: a case report].

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Ningxiang pig-derived Enterococcus hirae HNAU0516 ameliorates postweaning diarrhoea by promoting intestinal health and modulating the gut microbiota in piglets.

Early weaning-induced stress precipitates diarrhoea, significantly curtailing the growth performance of piglets. A pivotal contributor to this postweaning affliction is the emergence of gut bacterial dysbiosis. Enterococcus hirae, a promising probiotic, has indicated unclear effects and mechanisms on intestinal health. In this study, we investigated the effects and underlying mechanisms of oral supplementation with Ningxiang pig-derived Enterococcus hirae HNAU0516 orally supplementation on the gut bacterial community, immune response and gut barrier function in piglets. 21 d age Duroc × (Landrace × Yorkshire) piglets with a similar BW were randomly allocated to two groups. The Enterococcus hirae HNAU0516 administration group was inoculated orally with Ningxiang pig-derived Enterococcus hirae HNAU0516 throughout the trial period. Conversely, the control group received the same volume of physiological saline. Our findings revealed that Enterococcus hirae HNAU0516 supplementation effectively reduced diarrhoea rates of piglets (P = 0.010). Notably, this probiotic promoted intestinal development and enhanced intestinal barrier function. It also showed potential anti-inflammatory properties. Furthermore, Enterococcus hirae HNAU0516 supplementation significantly remodelled the colonic microbiota and increased the production of acetate (P = 0.007). In conclusion, our study highlights that Ningxiang pig-derived Enterococcus hirae HNAU0516 improves postweaning diarrhoea by promoting intestinal development, enhancing intestinal barrier function, decreasing intestinal permeability, modulating intestinal microbiota, and increasing short-chain fatty acids production.

Six1 Regulates Mouse Incisor Development by Promoting Dlx1/2/5 Expression.

Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. Six1, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs Six1 deletion mouse models to elucidate the critical regulatory role of Six1 in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that Dlx1, Dlx2, and Dlx5 (Dlx1/2/5) may function as the key TFs that promote the formation of DP. We further show that the deletion of Six1 perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of Dlx1/2/5 to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil Six1's indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.

A nomogram for predicting the overall survival in rectal cancer patients after total neoadjuvant therapy.

BACKGROUND: Total neoadjuvant therapy (TNT) has been recommended by the National Comprehensive Cancer Network for treating locally advanced rectal cancer (LARC), but extremely rare studies have focused on establishing nomograms to predict the prognosis in these patients after TNT. We aimed to develop a nomogram to predict overall survival (OS) in rectal cancer patients who underwent TNT. METHODS: In retrospective cohort study, we extract the data of the rectal cancer patients from the SEER database between 2010 and 2015, including demographic information and tumor characteristics. The cohort was divided into training set and validation set based on a ratio of 7:3. Univariate logistic regression analysis was utilized for the comparison of variables in training set. Candidate variables with P < 0.1 in training set was entered into the best subset selection, LASSO regression and Boruta feature selection. Finally, the selected variables significantly associated with the 3-year, 5-year, and 8-year OS were used to build a nomogram, followed by validation using receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration curve. RESULTS: A total of 3265 rectal cancer patients (training set: 2285; test set: 980) were included in the present study. A nomogram was developed to predict the 3-year, 5-year, and 8-year OS based on age, household income, total number of in situ/malignant tumors, CEA, T stage, N stage and perineural invasion. The nomogram showed good efficiency in predicting the 3-year, 5-year and 8-year OS with good AUC for the training set and test set, respectively. CONCLUSION: We established a nomogram for predicting the 3-year, 5-year, and 8-year OS of the rectal cancer patients, which showed good prediction efficiency for the OS after TNT.

[The combined application of oligoclonal bands in cerebrospinal fluid and IgG intrathecal synthesis indicators and biochemical markers in the diagnosis of multiple sclerosis].

Objective: To establish and verify a diagnostic model for distinguishing multiple sclerosis (MS) from other neurological diseases with similar symptoms by usingcerebrospinal fluid oligoclonal band (CSF-OCB)combined with IgG intrathecal synthesis indicators and biochemical markers. Methods: Multiple sclerosis (MS) patients admitted to the Neurology Department of Beijing Tiantan Hospital affiliated with Capital Medical University from January 2014 to December 2022 were selected as the case group, while patients with similar neurological symptoms were selected as the control group. Using the case-control study design, a retrospective analysis was conducted on the detection of age, gender, oligoclonal bands in cerebrospinal fluid, IgG intrathecal synthesis indicators and biochemical indicators for all study subjects. The differential diagnosis model was determined by the multiple logistic regression analysis, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of the differential diagnosis model for neurological diseases with similar symptoms to MS and other conditions. Results: This study included 167 patients in the case group and 335 patients in the control group, of which 128 patients in the case group and 265 patients in the control group were used to construct the model, and 39 patients in the case group and 70 patients in the control group were used for model validation. The differential diagnostic model constructed by a multivariate logistic regression model was Y=0.871×CSF-OCB-0.051×CSFprotein-0.231×CSFchloride+1.183×gender-0.036×LDH+35.770. The model showed that the area under the curve, sensitivity and specificity were respectively 0.916, 87.3% and 87.6%. The Delong test results showed that the diagnostic efficacy of the model was significantly different from OCB, IgG intrathecal synthesis indicators, and OCB combined with IgG intrathecal synthesis indicators (P<0.05). The new model validation showed that the actual diagnostic consistency rate for the MS group was 84.6%, while the actual diagnostic consistency rate for the control group was 90.0%. Conclusion: This study combines OCB, IgG intrathecal synthesis indicators, and biochemical indicators to establish a diagnostic prediction model for neurological diseases with similar clinical symptoms in MS. This model may have good differential diagnostic value and can better assist clinical diagnosis in the early stages of disease progression in MS patients.

[Current status and prospects of clinical practice for arteriovenous graft in China].

The use of arteriovenous graft (AVG) fails to meet the clinical needs in China, although it is recommended by guidelines to be the alternative access for maintenance hemodialysis (MHD) patients. Patency and complication incidence of AVG reported by recent research is superior to traditional cognition, and thus AVG should be one of main types of access in our country. Personalized selection of proper patients and grafts may improve the outcomes of AVG. In the future, outcomes of AVG must be further improved by clinical research with accurate personalized selection, basic research of precise molecule target and innovation of graft materials.

[Efficacy and safety of early cannulation arteriovenous grafts for hemodialysis].

A total of 309 (138 males and 171 females) end-stage renal disease patients who underwent implantation of early cannulation arteriovenous grafts (Acuseal) for hemodialysis in Nanfang Hospital, Southern Medical University between December 2016 and May 2021 were retrospectively included. The age of patients was (61.5±10.3) years. There were 244 patients (119 males and 125 females) who received regular follow-up. During the follow-up period, 24 patients died. Perioperative complications included graft infection (4.5%, 11/244), hematoma (4.5%, 11/244) and steal syndrome (4.1%, 10/244). No seroma or anastomotic rupture occurred. The rates of the first postoperative puncture time within 24 h, 48 h and 72 h after implantation were 42.2%(103/244), 32.4% (79/244) and 16.4% (40/244), respectively. The Kaplan-Meier survival analysis showed that the primary patency rates at 6 months and 12 months were 66.5% and 48.4%, respectively, and the secondary patency rates at 6 months and 12 months were 96.7% and 91.8%, respectively. The current study indicates that the Acuseal graft is safe for vascular access in patients requiring hemodialysis, with satisfactory patency and acceptable complication rates at 1-year follow-up.

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network.

PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

[Clinical application of inferior pancreaticoduodenal artery management in laparoscopic pancreaticoduodenectomy].

Objective: To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD). Methods: This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery. Results: The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days). Conclusion: Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

[Study of the methotrexate loaded extracellular vesicles in the treatment of experimental periodontitis in mice].

Objective: To investigate the therapeutic effect of methotrexate loaded vesicles on experimental periodontitis in mice. Methods: Extracellular vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUC-MSC). Methotrexate loaded vesicles (MTX-EVs) were constructed, whose morphology and size were analyzed by using scanning electron microscopy and particle size analyzer. Western blotting was used to identify their surface specific proteins. C57BL/6J male mice of 4-5 weeks (provided by Experimental Animal Center of The Fourth Military Medical University) were selected, among which 8 were randomly selected by blind grasp method without treatment and fed normally as normal group, and others were induced to periodontitis models by local injection of lipopolysaccharide (LPS) into the periodontium. The LPS was injected once every day with a concentration of 2 g/L and a volume of 5 µl, lasting for two weeks. The mice with successfully induced periodontitis were randomly divided into 4 groups by blind grasping method, with 8 mice in each group. The LPS group was with no treatment, and the other three groups were treated with periodontal local injection of MTX, EVs or MTX-EVs, respectively. Two weeks later, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory cytokine interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) in gingival tissue. The amount of alveolar bone resorption of four groups was detected by using micro-CT scanning and HE staining. The expression proportion of the inflammatory factor in gingival tissue was analyzed by using flow cytometry. Results: The scanning electron microscopy results showed that EVs and MTX-EVs were circular or elliptical in shape. Dynamic light scattering (DLS) particle size analysis showed that the particle size of EVs was around 200 nm, while that of MTX-EVs was around 300 nm. The ELISA results showed IL-1ß levels in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (28.86±2.76), (51.50±2.04), (35.26±2.40), (45.49±2.04) and (35.77±3.49) ng/L. That is, the IL-1ß concentrations in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group (P<0.05); the mass concentration of IL-1ß in the LPS +MTX-EVs group was significantly lower than that in the LPS+EVs group (P<0.05). The concentrations of IL-6 in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (125.44±4.12), (221.64±10.59), (178.16±16.90), (181.09±18.22) and (170.15±9.04) ng/L, among which the concentration of IL-6 in the last three groups were significantly lower than that in the LPS group (P<0.05). The mass concentration of IL-6 in the LPS+MTX-EVs group was significantly lower than those in the LPS+MTX group and LPS+EVs group (P<0.05). The concentrations of TNF-α in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (320.27±38.68), (479.62±40.94), (342.18±25.89), (415.88±12.01) and (325.75±30.83) ng/L, among which the concentrations of last three groups were significantly lower than the LPS group (P<0.05); the mass concentration of TNF-α in the LPS+MTX-EVs group was significantly lower than those in the LPS+EVs group and LPS+MTX group (P<0.05). The micro-CT results showed that the distance of cement-enamel junction-alveolar bone crest (CEJ-ABC) of the first molar and root (M1R1) in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group of mice were (0.11±0.03), (0.28±0.02), (0.23±0.03), (0.20±0.04), and (0.18±0.03) mm, respectively. Compared with the LPS group, the CEJ-ABC of the M1R1 in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were inhibited to varied degrees with statistically significant differences (P<0.05). Among them, LPS+MTX-EVs group had the best bone resorption inhibitioin effect compared to LPS+MTX group and LPS+EVs group, and the differences were statistically significant (P<0.05). The flow cytometry results indicated that the proportion of interferon-γ (IFN-γ) positive cells was (11.77±1.02)% in the LPS group, (6.87±0.65)% in the LPS+EVs group, and (4.15±0.92)% in the LPS+MTX-EVs group, respectively. The proportions of IFN-γ positive cells in the LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group (P<0.05), while the ratio of IFN-γ positive cells in the LPS+MTX-EVs group was found significantly lower than that in the LPS+EVs group (P<0.05). Conclusions: MTX-EVs can effectively alleviate the periodontal local inflammatory environment and reduce bone resorption of alveolar bone in periodontitis model mice.