Expression patterns of interleukin-6 and microRNA-146A during orthodontic relapse in a rat model.

In this study, we established an experimental rat model to simulate orthodontic tooth movement relapse and a human periodontal ligament stem cell (PDLScs) model. Our aim was to explore the relationship between microRNA-146a (miR-146a) expression in periodontal tissue, the inflammatory factor interleukin-6 (IL-6), and orthodontic relapse subsequent to mechanical intervention. In the animal experiment, a total of 30 healthy male Wistar rats were randomly allocated to either the control group (n=6) or the model group (n=24). In the model group, the orthodontic appliance was removed 14 days after force application. Gingival crevicular fluid (GcF) and periodontal tissue samples were collected at intervals of days 0, 7, 14, and 21 following removal of the orthodontic appliance to assess alterations in miR-146a and IL-6 expressions. In the in vitro cell culture study, human premolar tooth tissue was isolated 24 hours following the addition of the transfection reagent to harvest PDLScs. Reverse transcription quantitative polymerase chain reaction was employed to evaluate the expression levels of the miRNA-146a gene, while Western blot analysis was utilized to assess the production of the IL-6 protein. As a result in comparison to the control group, the protein expression of IL-6 notably escalated to its peak value in the model-day 7 group (p<0.05). Subsequently, although experiencing a slight decline, the IL-6 expression in the model-day 14 group remained significantly elevated compared to control group (p<0.05). In the model-day 21 group, the protein expression of IL-6 approached that of the control group, with no significant difference observed (p>0.05). conversely, in relation to the control group, the gene expression of miR-146a drastically decreased to its lowest point in the model-day 7 group (p<0.05). While exhibiting a slight increase, the miR-146a expression in the model-day 14 group remained significantly diminished compared to control group (p<0.05). Following the identification of human periodontal ligament cells (hPDLcs) through immunofluorescence in the in vitro study, a subsequent experiment was conducted to specifically inhibit miR-146a expression. In comparison to the control group, the protein expression of IL-6 demonstrated a significant increase in the anti-miRNA oligodeoxyribonucleotide (AMO) group, where miR-146a expression was effectively suppressed (p<0.05). Throughout the process of orthodontic tooth movement relapse in rats, there was a notable reduction in the gene expression of miR-146a, accompanied by a significant increase in the expression of IL-6.

[Clinical analysis on the impact of pretransplant iron overload on allogeneic hematopoietic stem cell transplantation for patients with acquired severe aplastic anemia in pediatric].

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children's Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 µg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34(+) cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.

[Analysis of pediatric heart transplantation supported by extracorporeal membrane oxygenation].

Objective: To summarize the clinical characteristics of patients with end-stage heart failure who receive heart transplant under extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data of 12 pediatric patients who received heart transplant with ECMO support in the Seventh Medical Center of Chinese People's Liberation Army General Hospital and Guangdong Provincial People's Hospital, from January 2019 to December 2023 was collected. The data included sex, age, weight, diagnosis, pre-ECMO lactate level, left ventricular ejection fraction (LVEF), vasoactive-inotropic score (VIS), and preoperative ECMO running time. Surgical data included cold ischemia time of the donor heart, cardiopulmonary bypass time, intraoperative use of immunosuppressant, postoperative use of ECMO, duration of postoperative ECMO, rate of successful weaning from ECMO, and survival discharge rate. The paired t-test was performed to compare cardiac function indices before and after left ventricular decompression. Results: The 12 patients ranged in age from 1.1 to 15.8 years, and weighted from 8 to 63 kg. Ten children were diagnosed with dilated cardiomyopathy, one with myocardial underdensification, and one with a novel heterozygous mutation of the SCN5A gene causing overlap syndrome complicated by fatal arrhythmia. Before ECMO, the lactate ranged from 0.6 to>15.0 mmol/L, the LVEF from 6.5% to 43%, and VIS from 3 to 108. Four patients underwent left ventricular decompression supported by preoperative ECMO, and their pulse pressure was significantly increased after decompression ((17.8±2.1) vs. (9.8±1.5) mmHg, 1 mmHg=0.133 kPa, t=11.31, P=0.001), while there was no apparent change in LVEF ((26.8±4.4)% vs. (24.9±4.9)%, t=1.75, P=0.178). A total of 7 children received a second run of ECMO after surgery and 3 of them successfully weaned off ECMO and survived to discharge. In the entire cohort, 10 were successfully weaned from ECMO and 8 survived to discharge. Conclusions: For children with end-stage heart failure supported by ECMO, left ventricular decompression can significantly improve pulse pressure. These patients will eventually require heart transplantation.

Unusual hard metal lung disease: bronchiolocentric interstitial pneumonia.

A 38-year-old woman experienced a persistent dry cough and progressively worsening dyspnoea for 2 years. Spirometry testing revealed a moderate-to-severe restrictive abnormality. High-resolution chest computed tomography showed diffuse reticulonodular opacities. A lung biopsy disclosed alveolar parenchymal inflammation and fibrosis with bronchiolocentric features, prompting consideration of interstitial pneumonia. Following a thorough investigation of her occupational history and an on-site inspection, it was discovered that the patient had been grinding drill bits designed for printed circuit boards for 8 years, exposing her to hard metals. Mineralogical analyses confirmed excessive tungsten in urine, serum and hair, leading to a diagnosis of hard metal lung disease due to tungsten carbide-cobalt exposure. After discontinuing exposure and commencing corticosteroid therapy, her symptoms, pulmonary function and imaging showed modest improvement. This case highlights the significance of assessing occupational history in patients with interstitial pneumonia and understanding industrial hazards for accurate diagnosis and care.

Exploring Putative Causal Associations between Diet and Periodontal Disease Susceptibility.

INTRODUCTION: Dietary factors may play an important role in periodontal health. However, current evidence from observational studies remains inconclusive. OBJECTIVE: This study aimed to investigate the causal relationships between dietary exposures and periodontal disease risks using Mendelian randomization analysis. METHODS: Large-scale genome-wide association study summary statistics for 20 dietary factors were obtained from the MRC-IEU consortium. Multivariable and univariable 2-sample Mendelian randomization analyses were performed to assess the causal effects of each dietary exposure on 6 periodontal outcomes, including gingivitis and periodontitis. RESULTS: Genetically predicted higher dried fruit intake was significantly associated with reduced risks of acute gingivitis (odds ratio [OR]: 0.02; 95% confidence interval [CI]: 0.00-0.42; P = 0.01) and bleeding gums (OR: 0.96; 95% CI: 0.93-0.99; P = 0.01). Higher fresh fruit and water intake showed protective effects against chronic gingivitis (OR: 0.18; 95% CI: 0.04-0.91; P = 0.04 and OR: 0.15; 95% CI: 0.04-0.53; P = 0.00) and bleeding gums (OR: 0.95; 95% CI: 0.92-0.981; P = 0.00 and OR: 0.98; 95% CI: 0.96-0.99; P = 0.02). Alcohol intake frequency and processed meat intake were risk factors for bleeding gums (OR: 1.01; 95% CI: 1.00-1.02; P = 0.01 and OR: 1.05; 95% CI: 1.01-1.08; P = 0.00) and painful gums (OR: 1.01; 95% CI: 1.00-1.01; P = 0.00 and OR: 1.02; 95% CI: 1.01-1.03; P = 0.00). Most of the causal relationships between genetic predisposition to the specified dietary factors and periodontal diseases remained statistically significant (P < 0.05) after adjusting for genetic risks associated with dentures, smoking, and type 2 diabetes in multivariable Mendelian randomization models. CONCLUSIONS: The findings suggest potential protective effects of higher fruit and water intake against gingivitis and other periodontal problems, while alcohol and processed meat intake may increase the risks of periodontal disease. Our study provides preliminary causal evidence on the effects of diet on periodontal health and could inform prevention strategies targeting dietary habits to improve oral health. KNOWLEDGE TRANSFER STATEMENT: This study suggests that fruit and water intake may protect against periodontal disease, while alcohol and processed meats increase risk, informing dietary guidelines to improve oral health.

Clinical value of deep learning image reconstruction on the diagnosis of pulmonary nodule for ultra-low-dose chest CT imaging.

PURPOSE: To compare the image quality and pulmonary nodule detectability between deep learning image reconstruction (DLIR) and adaptive statistical iterative reconstruction-Veo (ASIR-V) in ultra-low-dose CT (ULD-CT). METHODS: 142 participants required lung examination who underwent simultaneously ULD-CT (UL-A, 0.57 ± 0.04 mSv or UL-B, 0.33 ± 0.03 mSv), and standard CT (SDCT, 4.32 ± 0.33 mSv) plain scans were included in this prospective study. SDCT was the reference standard using ASIR-V at 50% strength (50%ASIR-V). ULD-CT was reconstructed with 50%ASIR-V, DLIR at medium and high strength (DLIR-M, DLIR-H). The noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective scores were measured. The presence and accuracy of nodules were analyzed using a combination of a deep learning-based nodule evaluation system and a radiologist. RESULTS: A total of 710 nodules were detected by SDCT, including 358 nodules in UL-A and 352 nodules in UL-B. DLIR-H exhibited superior noise, SNR, and CNR performance, and achieved comparable or even higher subjective scores compared to 50%ASIR-V in ULD-CT. Nodules sensitivity detection of 50%ASIR-V, DLIR-M, and DLIR-H in ULD-CT were identical (96.90%). In multivariate analysis, body mass index (BMI), nodule diameter, and type were independent predictors for the sensitivity of nodule detection (p<.001). DLIR-H provided a lower absolute percent error (APE) in volume (3.10% ± 95.11% vs 8.29% ± 99.14%) compared to 50%ASIR-V of ULD-CT (P<.001). CONCLUSIONS: ULD-CT scanning has a high sensitivity for detecting pulmonary nodules. Compared with ASIR-V, DLIR can significantly reduce image noise, and improve image quality, and accuracy of the nodule measurement in ULD-CT.

[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Body mass index’s effect on CRSwNP extends to pathological endotype and recurrence.

BACKGROUND: Elevated body mass index (BMI) has been recognized as an important contributor to corticosteroid insensitivity in chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to delineate the effects of elevated BMI on immunological endotype and recurrence in CRSwNP individuals. METHODOLOGY: A total of 325 patients with CRSwNP undergoing FESS were recruited and stratified by BMI. H&E staining was employed for histological evaluation. Characteristics of inflammatory patterns were identified by immunohistochemical staining. The predictive factors for recurrence were determined and evaluated by multivariable logistic regression analysis and the receiver operating characteristic (ROC) curves across all subjects and by weight group. RESULTS: In all patients with CRSwNP, 26.15% subjects were classified as overweight/obese group across BMI categories and exhibited a higher symptom burden. The upregulated eosinophil/neutrophil-dominant cellular endotype and amplified type 2/ type 3 coexisting inflammation was present in overweight/obese compared to underweight/normal weight controls. Additionally, a higher recurrent proportion was shown in overweight/obese patients than that in underweight/normal weight cohorts. Multivariable logistic regression analysis identified BMI as an independent predictor for recurrence. The predictive capacity of each conventional parameter (tissue eosinophil and CLCs count, and blood eosinophil percentage) alone or in combination was poor in overweight/obese subjects. CONCLUSIONS: Overweight/obese CRSwNP stands for a unique phenotype and endotype. Conventional parameters predicting recurrence are compromised in overweight/obese CRSwNP, and there is an urgent need for novel biomarkers that predict recurrence for these patients.

[Role and related mechanisms of LiaSR two-component system in acid tolerance and biofilm formation of Streptococcus mutans].

Objective: To investigate the role and related mechanisms of the LiaSR two-component system in acid tolerance and biofilm formation abilities of Streptococcus mutans (Sm) 593. Methods: The growth curves of various Sm strains in pH=5.5 brian heart infusion (BHI) medium were analyzed. And colony forming unit (CFU) was also performed to evaluate the acid tolerance of Sm. Laurdan probe, H+-K+adenosine triphosphate (ATP)ase activity analysis kit, proton permeability assay and real-time fluorescence quantitative PCR (RT-qPCR) were conducted to detect the acid tolerant mechanisms of LiaSR two-component system in Sm. Crystal violet staining, CFU, SYTOX probe and anthrone-sulfuric method were used to analyze the properties and structures of the Sm biofilms. RT-qPCR was conducted to detect the expression levels of underlying regulated genes. Results: The growth of mutants in acidic BHI were inhibited (P<0.05). The acid tolerance of mutants significantly decreased compared to the wild-type strain (P<0.05). In mutants, the activity of H+-ATPase (917.06±59.53 and 469.53±47.65) were elevated by 7.22-folds and 3.70-folds compared to the wild-type strain (127.00±50.71) (P<0.001, P<0.001) and the encoded gene atpD (3.39±0.21 and 1.94±0.17) were also elevated by 3.39-folds and 1.94-folds compared to the wild-type strain (1.00±0.15) (P<0.001, P=0.001). The Laurdan generalized polarization of mutants (0.18±0.04 and 0.18±0.05) increased significantly compared to the wild-type strain (0.08±0.05) (P=0.006, P=0.003) and the expression levels of fabM gene were decreased in mutants (0.52±0.11 and 0.57±0.05) by 1/2 (P=0.014, P=0.022). In liaR deletion mutant, the reduced terminal pH (4.76±0.01) can also be observed (P<0.001). The total amount of the biofilms of three Sm didn't show significant differences (P>0.05). But the number of viable bacteria of mutants' biofilms were decreased [Sm 593: (12.00±2.80)×107 CFU/ml; Sm ΔliaS: (2.95±1.13)×107 CFU/ml; Sm ΔliaR: (7.25±1.60)×107 CFU/ml] (P=0.001, P=0.024). The extracellular DNA were increased by 18.00-folds and 6.50-folds in mutants' biofilms (128.73±15.65 and 46.38±5.52) compared to the wild-type strain (7.16±3.62) (P<0.001, P=0.003). Water-soluble exopolysaccharides could be found up-regulated in liaS deletion mutant [(138.73±10.12) µg/ml] (P=0.003) along with the expression level of gtfC gene (1.65±0.39) (P=0.014). The expression level of gtfD were elevated by 47.43-folds and 16.90-folds in mutants (P<0.001, P=0.010). Conclusions: The LiaSR two-component system can promote the expression of fabM gene and increase the fluidity of Sm which contributes to acid tolerance. The LiaR can also decrease the proton permeability and restrict the entrance of H+. The LiaSR two-component system can negatively regulate the production of the extracellular matrix in Sm biofilm.

[Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center].

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

[Clinical effects of free superficial circumflex iliac artery superficial branch perforator flap combined with full-thickness skin graft far from the flap donor site in repairing the large wounds in extremities].

Objective: To investigate the clinical effects of free superficial circumflex iliac artery (SCIA) superficial branch perforator flap combined with full-thickness skin graft far from the flap donor site in repairing the large wounds in extremities. Methods: The study was a retrospective observational study. From January 2020 to June 2022, 19 patients with large wounds in extremities who met the inclusion criteria were admitted to the First Affiliated Hospital of Bengbu Medical College, including 15 males and 4 females, aged 28-75 years. The debridement, fracture reduction and fixation, tendon, vessel, and nerve repair, and vacuum sealing drainage were performed in the first stage surgery. After debridement in the second stage surgery, the total wound area was 13.0 cm×8.0 cm-34.0 cm×15.0 cm. The tendon and bone exposed wound with area of 9.0 cm×6.0 cm-14.0 cm×7.0 cm was repaired with free SCIA superficial branch perforator flap with area of 10.0 cm×6.5 cm-15.0 cm×8.0 cm. The remaining granulation tissue wound with area of 5.0 cm×3.5 cm-13.0 cm×8.0 cm was repaired with full-thickness skin graft far from the flap donor site with area of 5.0 cm×3.5 cm-13.0 cm×8.0 cm. All the wounds in donor site were sutured. The operation time and amount of bleeding of patients during the surgery were recorded, the survival of flap and skin graft were observed after surgery. During follow-up, the flap and skin graft, scar in the donor site and its effect on donor site function were observed. At the last follow-up, the satisfaction of patients with the efficacy was evaluated by the efficacy satisfaction rating score. Results: The operation time of patients was 2.0-3.5 h. The amount of bleeding of patients during the surgery was 100-320 mL. One patient had ecchymosis and venous crisis in the edge of flap on the second day after surgery, and the flap survived after exploration. The flaps of the other patients survived smoothly. The skin grafts of patients all survived smoothly. Two patients had bloated flaps due to obesity in the later stage, and the expected results were achieved after flap thinning surgery 6 months after operation. During the follow-up of 6 to 24 months, the flaps had good elasticity and soft texture, and the skin grafts had no wear or ulceration; linear scars were left in all the donor sites but their functions were not affected. The patients were all satisfied with the efficacy. Conclusions: Free SCIA superficial perforator flap combined with full-thickness skin graft far from the donor site was used to repair the large wounds in extremities, which was safe, reliable, and less traumatic and short in operation time, and resulted in good postoperative appearance and function in the donor sites and recipient sites.

[Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage â ovarian immature teratoma after fertility-sparing surgery].

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a disease caused by insufficient blood supply in the brain in newborns during the perinatal period. Severe HIE leads to patient death, and patients with mild HIE are at increased risk of cognitive deficits and behavioral abnormalities. The NMDA receptor is an important excitatory receptor in the central nervous system, and in adult hypoxic-ischemic injury both subtypes of the NMDA receptor play important but distinct roles. The GluN2A-containing NMDA receptor (GluN2A-NMDAR) could activate neuronal protective signaling pathway, while the GluN2B-NMDAR subtype is coupled to the apoptosis-inducing signaling pathway and leads to neuronal death. However, the expression level of GluN2B is higher in newborns than in adults, while the expression of GluN2A is lower. Therefore, it is not clear whether the roles of different NMDA receptor subtypes in HIE are consistent with those in adults. We investigated this issue in this study and found that in HIE, GluN2B plays a protective role by mediating the protective pathway through binding with PSD95, which is quite different to that in adults. The results of this study provided new theoretical support for the clinical treatment of neonatal hypoxic ischemia.

[Preliminary progress in the study of the relationship between COVID-19 infection and partial arterial or venous diseases].

Vascular complications are commonly associated with COVID-19 infection. Increasing reports suggest a close relationship between COVID-19 and venous thromboembolic diseases, including deep vein thrombosis and pulmonary embolism. Furthermore, COVID-19 has been linked to various aortic diseases such as aortic valve stenosis, aortic thrombosis, abdominal aortic aneurysm, aortic dissection, and limb ischemia. Consequently, understanding the causes and treatment of these vascular complications has become a critical aspect of comprehensive COVID-19 management. This article provides a review of aortic diseases and venous thromboembolic diseases that may be associated with COVID-19, aiming to explore potential mechanisms underlying the development of these vascular conditions and discuss strategies for preventing thrombosis in COVID-19 patients.

[JAG1 affects monocytes-macrophages to reshape the pre-metastatic niche of triple-negative breast cancer through LncRNA MALAT1 in exosomes].

OBJECTIVE: To investigate the effect of JAG1 on the activities of monocytes-macrophages in pre-metastatic niche (PMN) of triple-negative breast cancer (TNBC) and explore the possible regulatory mechanism. METHODS: JAG1 expression in human TNBC MDA-MB-231 and MDA-MB-231B cells was detected using quantitative real-time PCR (qRT-PCR).Ten female nude mice were inoculated with MDA-MB-231 cells (n=5) or MDA-MB-231B cells (n=5) in the mammary fat pad, and 6 weeks later, the tumor tissues were collected for immunohistochemistry.Human monocytes THP-1 cells were treated with rhJAG1 or conditioned media (CM) of TNBC MDA-MB-231 and MDA-MB-231B cells to assess the direct effect of JAG1 on monocytes and its effect on monocytes in the PMN using monocyte-endothelial adhesion, Transwell assay, qRT-PCR and Western blotting.Transmission electron microscopy and nanoparticle tracking analyses were used to identify the effect of JAG1 on exosome release from the TNBC cells.MiRNAs interacting with lncRNA MALAT1 were identified by bioinformatics and validated using qRT-PCR. RESULTS: Compared with MDA-MB-231 cells, the invasive strain MDA-MB-231B cells showed significantly higher JAG1 expression and greater liver metastasis potential (P<0.01).Both direct treatment with rhJAG1 and treatment with the conditioned media promoted adhesion and migration and affected differentiation of the monocytes (P<0.05).Transmission electron microscopy and nanoparticle tracking analysis showed that JAG1 strongly enhanced exosome secretion from MDAMB-231 cells (P<0.01) and increased MALAT1 content in the exosomes (P<0.0001).Five candidate miRNAs related to MALAT1 and JAG1 were identified by bioinformatics analysis, and miR-26a-5p was identified as a potential target of MALAT1 in monocytes-macrophages in TMN (P<0.0001). CONCLUSION: JAG1 can promote exocrine secretion of TNBC and increase the expression of MALAT1 to cause targeted downregulation of miR-26a-5p in monocytes-macrophages in the PMN, which in turn increases JAG1 expression in monocytes-macrophages to affect their adhesion, migration and osteoclast differentiation in the PMN.

[Association of category of dietary intake and physical activity with the risk of mortality in patients with type 2 diabetes mellitus: a prospective cohort study].

Objective: To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM). Methods: Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM. Results: As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio (HR)=0.81, 95%CI: 0.70-0.94] and a 33% lower risk of all-cause mortality (HR=0.67, 95%CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% (HR=0.50, 95%CI: 0.45-0.56), 50% (HR=0.50, 95%CI: 0.41-0.61), and 27% (HR=0.73, 95%CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% (HR=0.45, 95%CI: 0.38-0.53), 56% (HR=0.44, 95%CI: 0.32-0.59), and 40% (HR=0.60, 95%CI: 0.44-0.82), respectively. Conclusion: Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

The feasibility and safety of laparoscopic inguinal hernia repair as a 24-h day surgery for patients aged 80 years and older: a retrospective cohort study.

INTRODUCTION: As the proportion of aging adults increases and inguinal hernia repair becomes increasingly popular as a day surgery, the demand for laparoscopic inguinal hernia repair as a day surgery is increasing among patients aged 80 years and older. Relevant research needs to be completed, so we aimed to evaluate laparoscopic inguinal hernia repair as a 24-h day surgery for this group of patients. METHODS: In this retrospective cohort study, we utilized propensity score matching to analyze the data of patients who underwent laparoscopic inguinal hernia repair at a day surgery center between January 1, 2019, and March 1, 2022. Patients were divided into ≥ 80 years old and < 80 years old groups. We compared the perioperative laboratory results, perioperative outcomes, and 1-year complications between the two groups. RESULT: A total of 554 patients were included in the study. After propensity score matching, 292 patients were included in the matched cohort (98 patients in the ≥ 80 years old group and 194 patients in the < 80 years old group). During hospitalization, there were significant differences in ASA classification, Caprini score, length of hospital stays, risk of thrombosis, and delayed discharge rate. No significant difference was found in the incidence of total postoperative complications between the two groups at the 1-year follow-up (HR: 0.96, 95% CI 0.36-2.54, P = 0.96). CONCLUSION: In our study, LIHR as a 24-h day surgery was safe and effective for patients over 80 years old. However, to reduce the rate of delayed discharge, cautious perioperative evaluation is necessary.

[A single-center retrospective study of percutaneous drainage clinical characteristics of grade B and C postoperative pancreatic fistula and determination of the optimal intervention time].

Objective: To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow. Methods: Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher's exact test between the two groups. Results: Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21),χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay(M(IQR))(24(20)days vs. 39(53)days,Z=3.023,P=0.003). Conclusions: The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.