[Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures].

OBJECTIVE: To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture. METHODS: From January 2017 to March 2022, 11 patients with infected anterior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 females and the age ranged from 27 to 49 years old. The pelvic fractures were classified according to the Tile typology: 4 cases of C1 type, 4 cases of C2 type, and 3 cases of C3 type. Among them, 2 cases of infected anterior ring were infected after internal fixation of anterior ring, and 9 patients were infected with infected anterior ring due to incomplete early debridement, which was classified as infected according to the injury severity score(ISS) for 24 to 38 scores. The anterior ring was internally fixed by extended debridement, irrigation, and antibiotic bone cement covered reconstruction plate, and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws. RESULTS: All 11 cases obtained follow-up from 13 to 20 months. Among them, 2 patients had recurrence of postoperative infection, 1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation, and 1 case had a milder infection without accumulation of the medullary cavity, and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting. Two cases developed incisional oozing, which healed after removal of the internal fixation three months postoperatively. All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period. All 11 cases eventually healed bony. At the final follow-up, according to the Matta score, the fracture reduction was excellent in 6 cases, good in 4, and possible in 1. According to the Majeed functional score, it was excellent in 6, good in 3, and possible in 2. CONCLUSION: Antibiotic bone cement covered reconstruction plate is effective in the treatment of infected anterior pelvic ring fracture, with high intraoperative safety and low recurrence rate of infection, which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.

Molecular Advances of Bud Dormancy in Trees.

Seasonal bud dormancy in perennial woody plants is a crucial and intricate process that is vital for the survival and development of plants. Over the past few decades, significant advancements have been made in understanding many features of bud dormancy, particularly in model species, where certain molecular mechanisms underlying this process have been elucidated. In this review, we provide an overview of recent molecular progress in understanding bud dormancy in trees, with a specific emphasis on the integration of common signaling and molecular mechanisms identified across different tree species. Additionally, we address some challenges that have emerged in the in-depth understanding of bud dormancy and offer insights for future studies.

The Amino Acid Transporter PtCAT7 and Ammonium Nutrition Enhance the Uptake of Thiamethoxam in Citrus Rootstock Seedlings.

Thiamethoxam (THX), when applied to the soil, can be taken up by citrus roots and subsequently transported to the leaves, providing effective protection of plants against the Asian citrus psyllid (Diaphorina citri Kuwayama). In this study, the field experiments showed that the coapplication of THX and nitrogen fertilizer (AN) did not affect THX uptake in six-year-old citrus plants. However, their coapplication promoted THX uptake in three-year-old Potassium trifoliate rootstocks and relieved the inhibition of AN at a higher level on plant growth characteristics, including biomass and growth of root and stem. RNA-seq analysis found that THX induced upregulation of a cationic amino acid transporter (PtCAT7) in citrus leaves. PtCAT7 facilitated THX uptake in the yeast strain to inhibit its growth, and the PtCAT7 protein was localized on the plasma membrane. Our results demonstrate that THX and N fertilizer can be coapplied and PtCAT7 may be involved in THX uptake in citrus.

Pregnancy outcomes and birth defects in offspring following Non-steroidal anti-inflammatory drugs exposure during pregnancy: A systematic review and meta-analysis.

There is a high global prevalence of NSAIDs during pregnancy. However, current evidence is largely conflicting regarding the safety of gestational NSAIDs use both for the pregnancy and offspring health. The aim of this study is to systematically review the relationship between NSAIDs use during pregnancy and the risk of adverse pregnancy outcomes and congenital abnormalities. Cohort studies and case control studies on congenital malformations, miscarriage and preterm birth in infants born to mothers who were exposed to NSAIDs during pregnancy were identified via PubMed, Medline, Embase, the Cochrane Library databases and the Reprotox® database from inception to 26 March 2021, and updated on 6 April 2023. On the whole, compared with the unexposed group, infants exposed to NSAIDs during early pregnancy showed a 28% increased risk of overall congenital anomalies (OR 1.28, 95%CI 1.16-1.40), and 19% for major birth defects (OR 1.19, 95%CI 1.08-1.30). Contrary to previous beliefs, there appeared to be a trend towards a higher risk of miscarriage among women who were exposed to NSAIDs during pregnancy, but the association was not statistically significant (OR 1.20, 95%CI 0.93-1.55). According to our study findings, the use of NSAIDs by pregnant women has been linked to a higher risk of congenital anomalies and a negative impact on preterm birth. Therefore, we advise pregnant women to carefully consider the potential benefits and risks before using NSAIDs during pregnancy.

[Limited internal fixation combined with a hinged external fixator in treatment of peri-elbow bone infection].

Objective: To evaluate the effectiveness of limited internal fixation combined with a hinged external fixator in the treatment of peri-elbow bone infection. Methods: The clinical data of 19 patients with peri-elbow bone infection treated with limited internal fixation combined with a hinged external fixator between May 2018 and May 2021 were retrospectively analyzed. There were 15 males and 4 females with an average age of 44.6 years (range, 28-61 years). There were 13 cases of distal humerus fractures and 6 cases of proximal ulna fractures. All the 19 cases were infected after internal fixation of fracture, and 2 cases were complicated with radial nerve injury. According to Cierny-Mader anatomical classification, 11 cases were type Ⅱ, 6 cases were type Ⅲ, and 2 cases were type Ⅳ. The duration of bone infection was 1-3 years. After primary debridement, the bone defect was (3.04±0.28) cm, and the antibiotic bone cement was implanted into the defect area, and the external fixator was installed; 3 cases were repaired with latissimus dorsi myocutaneous flap, and 2 cases were repaired with lateral brachial fascial flap. Bone defects repair and reconstruction were performed after 6-8 weeks of infection control. The wound healing was observed, and white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were reexamined regularly after operation to evaluate the infection control. X-ray films of the affected limb were taken regularly after operation to observe the bone healing in the defect area. At last follow-up, the flexion and extension range of motion and the total range of motion of the elbow joint were observed and recorded, and compared with those before operation, and the function of the elbow joint was evaluated by Mayo score. Results: All patients were followed up 12-34 months (mean, 26.2 months). The wounds healed in 5 cases after skin flap repair. Two cases of recurrent infection were effectively controlled by debridement again and replacement of antibiotic bone cement. The infection control rate was 89.47% (17/19) in the first stage. Two patients with radial nerve injury had poor muscle strength of the affected limb, and the muscle strength of the affected limb recovered from grade Ⅲ to about grade Ⅳ after rehabilitation exercise. During the follow-up period, there was no complication such as incision ulceration, exudation, bone nonunion, infection recurrence, or infection in the bone harvesting area. Bone healing time ranged from 16 to 37 weeks, with an average of 24.2 weeks. WBC, ESR, CRP, PCT, and elbow flexion, extension, and total range of motions significantly improved at last follow-up ( P<0.05). According to Mayo elbow scoring system, the results were excellent in 14 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 89.47%. Conclusion: Limited internal fixation combined with a hinged external fixator in the treatment of the peri-elbow bone infection can effectively control infection and restore the function of the elbow joint.

Corrigendum: Pre-transplant CRP-albumin ratio as a biomarker in patients receiving haploidentical allogeneic hematopoietic transplantation: developing a novel DRCI-based nomogram.

[This corrects the article DOI: 10.3389/fimmu.2023.1128982.].

Pre-transplant CRP-albumin ratio as a biomarker in patients receiving haploidentical allogeneic hematopoietic transplantation: Developing a novel DRCI-based nomogram.

Background: In allogeneic hematopoietic stem cell transplantation (allo-HSCT), prognostic indicators effectively predict survival. The Disease conditions prior to transplantation dramatically affects the outcome of HSCT. Optimization of the pre-transplant risk assessment is critical for enhancing allo-HSCT decision-making. Inflammation and nutritional status play significant roles in cancer genesis and progression. As a combined inflammatory and nutritional status biomarker, the C-reactive protein/albumin ratio (CAR) can accurately forecast the prognosis in various malignancies. This research sought to examine the predictive value of CAR and develop a novel nomogram by combining biomarkers and evaluating their importance following HSCT. Methods: Analyses were conducted retroactively on a cohort of 185 consecutive patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) at Wuhan Union Medical College Hospital during the period from February 2017 to January 2019. Of these patients, 129 were randomly assigned to the training cohort, and the remaining 56 patients constituted the internal validation cohort. Univariate and multivariate analyses were carried out to examine the predictive significance of clinicopathological factors in the training cohort. Subsequently, the survival nomogram model was developed and compared with the disease risk comorbidity index (DRCI) using the concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curve, and decision curve analysis (DCA). Results: Patients were separated into low and high CAR groups using a cutoff of 0.087, which independently predicted overall survival (OS). Based on risk factors, CAR, the Disease Risk Index(DRI), and the Hematopoietic Cell Transplantation-specific Comorbidity Index(HCT-CI), the nomogram was developed to predict OS. The C-index and area under the ROC curve confirmed the improved predictive accuracy of the nomogram. The calibration curves revealed that the observed probabilities agreed well with those predicted by the nomogram in training, validation and entire cohort. It was confirmed by DCA that the nomogram offered greater net benefits than DRCI among all cohorts. Conclusion: CAR is an independent prognostic indicator for haplo-HSCT outcomes. Higher CAR was related to worse clinicopathologic characteristics and poorer prognoses in patients underwent haplo-HSCT. This research provided an accurate nomogram for predicting the OS of patients following haplo-HSCT, illustrating its potential clinical utility.

The relationship between non-alcoholic fatty liver disease and incidence of chronic kidney disease for diabetic and non-diabetic subjects: A meta-analysis.

INTRODUCTION: The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases. OBJECTIVES: The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control. MATERIAL AND METHODS: A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs). RESULTS: The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88). CONCLUSION: Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.

Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.

Retreatment of a C-shaped maxillary second molar: case reports and literature review.

The root canal systems of maxillary second molar (MSM) variations are complicated, especially the prevalence of fused roots and consequent merged and C-shaped canals, which represent a clinical challenge because canal configurations can be irregular and unpredictable. The purpose of this article was to present 2 cases with a C-shaped configuration diagnosed during root canal retreatment and perform a literature review of this MSM anatomy. Case 1 reports that two palatal root canals fused into a C-shaped configuration that finally formed an apical foramen, which was classified as Type D. Case 2 reflects the fusion of the distobuccal canal and palatal canal into a C-shaped configuration and the configuration was Type C, which was first reported in a case report. Nonsurgical retreatments were proposed and conducted. Evaluation at a 24-month recall revealed that the two patients were symptom-free, and radiographic examination revealed normal periapical tissue. This report serves to remind clinicians of the complexities of the root canal system and that possible anatomic variation should always be anticipated when formulating an effective root canal treatment plan. The use of CBCT imaging coupled with an operative dental microscope will be helpful in locating and identifying supernumerary canals when a preoperative periapical radiograph shows signs of a fused-rooted MSM.

Corrigendum: Myelodysplastic syndrome/acute myeloid leukemia following the use of poly-ADP ribose polymerase inhibitors: A real-world analysis of postmarketing surveillance data.

[This corrects the article DOI: 10.3389/fphar.2022.912256.].

Myelodysplastic Syndrome/Acute Myeloid Leukemia Following the Use of Poly-ADP Ribose Polymerase (PARP) Inhibitors: A Real-World Analysis of Postmarketing Surveillance Data.

Background and purpose: poly-ADP ribose polymerase (PARP) inhibitors show impressive efficacy in a range of tumors. However, concerns about rare and fatal adverse events, including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have arisen. The aim of this study was to excavate and evaluate the risk of PARP inhibitors causing MDS and AML based on real-world data from two international pharmacovigilance databases. Methods: We analyzed adverse event (AE) reports of four PARP inhibitors (olaparib, niraparib, rucaparib and talazoparib) associated with MDS and AML from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and EudraVigilance (EV) databases between 1 October 2014, and 30 September 2021, including demographic characteristics, fatality and times to onset. Three different data mining algorithms were used to detect the signals of PARP inhibitors associated with MDS and AML. Results: In total, 16,710 and 11,937 PARP inhibitor AE reports were found in the FAERS and EV databases, of which 332 and 349 were associated with MDS and AML, respectively. The median latencies of MDS and AML associated with PARP inhibitors were 211 [interquartile range (IQR) 93.5-491.25] days and 355 (IQR 72.00-483.50) days, respectively. The average fatality rates of MDS and AML caused by the four PARP inhibitors were 37.96 and 60.41%, respectively, in the FAERS database, while those in the EV database were 5.83 and 12.16%, respectively. Based on the criteria used for the three algorithms, a significant disproportionate association was found between PARP inhibitors as a drug class and MDS/AML. Notably, the risk of MDS was much higher than that of AML. Olaparib appeared to have a stronger association with MDS and AML than did other PARP inhibitors. Conclusion: In the real world, PARP inhibitors increase the risk of MDS and AML, which can result in high mortality and tend to occur during long-term use. Our findings provide objective evidence for the postmarketing safety of PARP inhibitors.

A large-scale study of patients with preoperative vocal cord paralysis associated with thyroid disease and related clinicopathological features.

BACKGROUND: The performance of thyroidectomies has been increasing over the last decade due to the growing prevalence of thyroid diseases. The purpose of this study was to investigate the clinical significance of preoperative vocal cord paralysis (VCP) associated with thyroid disease and other incidences of malignant or benign lesions, as well as different thyroid pathological features. Additionally, the epidemiological changes of thyroid diseases with preoperative VCP were investigated. METHODS: Ninety-nine out of 12,530 patients with preoperative VCP who had undergone thyroid surgery for various diseases in the Zhejiang Cancer Hospital from January 2007 to December 2015 were identified. Their clinicopathological data was recorded and case distributions from different years and intraoperative recurrent laryngeal nerve statuses were retrospectively analyzed. RESULTS: The incidence of preoperative VCP in 2007 was reported to be 1.53% (9/590) and had decreased to 0.53% (12/2,247) by 2015 (P < 0.05). Among the 99 patients with preoperative VCP, 81 had malignancies (81.82%), while 18 (18.18%) had benign thyroid diseases. The incidences of preoperative VCP in malignant and benign diseases were 1.13% (81/7,159) and 0.35% (18/5,371), respectively (P < 0.05). There were only 5 (0.04%, 5/12,530) cases of papillary thyroid microcarcinoma with preoperative VCP. There was no statistical difference between the incidence of preoperative hoarseness in malignant 69.14% (56/81) and benign diseases 61.11% (11/18) with preoperative VCP. CONCLUSIONS: The preoperative VCP incidence rate had gradually decreased with an increased proportion of papillary thyroid cancer. Preoperative voice symptoms do not necessarily suggest a malignancy. Selective rather than routine preoperative laryngoscopic examinations should be performed on papillary thyroid microcarcinomas. The probability of preoperative VCP in malignancy was significantly higher than in benign lesions.

Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF-κB Signaling Pathway.

Objective: To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods: Rats were randomly divided into 4 groups: control group (n = 6) were injected with the same amount of normal saline; ALF group (n = 10) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 µg/kg); ALF+JDHY group (n = 10) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group (n = 10) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1ß, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results: JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly (P < 0.01), increase PTA and PLT (P < 0.01), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased (P < 0.01). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1ß, and TNF-α while increasing the level of IL-10 and IL-13 (P < 0.01). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased (P < 0.01). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKßα, and IKKß in the ALF rat tissues. Conclusions: JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

The Clinical Efficacy of Double Plasma Molecular Absorption System Combined with Plasma Exchange in the Treatment of Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

Objective: This study aims to investigate the clinical efficacy of plasma exchange in treating acute-on-chronic liver failure (ACLF) through meta-analysis. Method: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched using a computer for all relevant Chinese and English literature from 2000 to 2021 in each database. At the same time, a large number of related papers and materials were manually consulted. Randomized controlled trials of plasma exchange (PE, control group) and combined double plasma molecular absorption system (DPMAS + PE, observation group) for the treatment of ACLF were collected. Meta-analysis was performed with Stata16.0 software. Result: A total of 474 articles were retrieved, and 11 papers were finally included for research after screening. Meta-analysis results showed that the effective rate of treatment in the experimental group was significantly higher than that in the control group. At the same time, the observation group's prothrombin activity (PTA) level was better than that of the control group after treatment. After treatment, there was no significant difference in prothrombin time (PT) and international normalized ratio (INR) between the two groups. In addition, after treatment, the alanine aminotransferase (ALT) level of the observation group was significantly lower than that of the control group. However, TBIL levels and albumin (ALB) levels did not change significantly between the two groups. Regarding blood routine indexes, there were no significant changes in creatinine (Cr) levels and platelet counts (PLT) in the two groups after treatment, but hemoglobin (HGB) levels in the observation group were significantly lower than those in the control group. Conclusion: DPMAS combined with plasma exchange therapy can improve liver function, coagulation function, and blood routine level of ACLF patients and increase the effective rate of treatment. It is an effective treatment for acute-on-chronic liver failure.

miR-183-5p promotes proliferation, invasion, and glycolysis of thyroid carcinoma cells by targeting FOXO1.

The aim of this study was to research the influences of miR-183-5p on the proliferation, invasion, and glycolysis of thyroid cancer (THCA) cells. Clinical specimens from 84 THCA patients were included. THCA cell lines (K1, SW1736, and TPC1) were cultured. siFOXO1, miR-183-5p mimic, or miR-183-5p inhibitors were transfected into THCA cells by Lipofectamine ™ 2000. qRT-PCR, western blot, and immunohistochemistry assays were used to detect miR-183-5p and FOXO1 expression. CCK-8 assay, colony formation, flow cytometry, Transwell, and wound healing experiment were utilized, respectively, to detect cell proliferation, colony formation, apoptosis, invasion, and migration. Glycolysis was evaluated by detecting glucose uptake, lactate production, ATP level, and glycolysis-related proteins expression. Dual-luciferase reporter assay and RNA pull-down assay were employed to verify the target relationship between miR-183-5p and FOXO1. The effect of miR-183-5p on THCA cells growth in vivo was researched using nude mice. miR-183-5p was highly expressed in THCA tissues and cells, correlating with poor outcome. miR-183-5p up-regulation attenuated apoptosis, and accelerated proliferation, colony formation, migration, invasion, and glycolysis of THCA cells. Opposite results were found by miR-183-5p down-regulation. FOXO1 was a target gene of miR-183-5p, where expression was directly inhibited by miR-183-5p. FOXO1 silencing reversed the inhibitory effect of miR-183-5p inhibitor on THCA cells malignant phenotype. miR-183-5p down-regulation inhibited THCA cells growth in vivo. miR-183-5p accelerates progression and glycolysis of THCA by targeting FOXO1. miR-183-5p was a novel target for THCA treatment.

Combined expression of the BRAFV600E mutation and PD-L1 in early papillary thyroid carcinoma and its relationship with clinicopathological features and recurrence-a retrospective cohort study.

Background: Identifying the high recurrence group of patients with early-stage papillary thyroid cancer (PTC) is the greatest challenge in the management of this disease. It has been noted that B-type Rafkinase (BRAF) V600E mutation and programmed death ligand 1 (PD-L1) are associated in PTC and highly expressed in PTC, correlating in PTC as potential prognostic biomarkers. However, whether they can be used to predict the aggressiveness and recurrence of early PTC remains unclear. Methods: Clinicopathological data of 137 patients with early PTC [tumor-node-metastasis (TNM) stage I-II] who underwent surgery in Zhejiang Cancer Hospital between 2008 and 2010 were retrospectively analyzed. BRAFV600E mutation and PD-L1 was detected by immunohistochemistry. The median follow-up time was 136 months (interquartile range 5.8). The presence of tumor confirmed by imaging or pathology or lymph node metastasis was considered as tumor recurrence. The association of both alone and in combination with clinicopathological features and recurrence was statistically analyzed respectively. The risk of recurrence was assessed using Cox regression models. Results: Most of the 137 early PTC were female (78.1%). The mean age was 43.2±12.1 years. The median tumor size was 1.4 cm; 14 patients developed recurrence during follow-up period; 56 patients (40.9%) were detected positive for BRAFV600E mutation; 76 patients (55.5%) were detected positive for PD-L1. Patients with both BRAFV600E mutation and PD-L1 expression had larger tumors (P=0.038), were more likely to have extrathyroidal invasion (P=0.045), and had a lower rate of cervical lymph node metastasis (P=0.046). The recurrence rate was 17.5% (7/40) in patients with BRAFV600E mutation and PD-L1 double expression compared to 8.9% (4/45) in patients with BRAFV600E mutation and PD-L1 double negative [hazard ratio (HR) =1.267; 95% CI: 0.841-1.909; P=0.257]. Survival curves showed flatter recurrence-free survival (RFS) curves in positive BRAFV600E mutation only and PD-L1 expression only, whereas decreased sharply in positive expression of both BRAFV600E mutation and PD-L1; however, the differences were not significant (P>0.05). Conclusions: The combination of BRAFV600E mutation and PD-L1 to identify group at higher risk of recurrence in early PTC has insufficient clinical evidence and should be used with caution in the clinical management of PTC.

Biodegradable iron oxide nanoparticles for intraoperative parathyroid gland imaging in thyroidectomy.

Parathyroid gland (PG) injury is the most common complication of thyroidectomy owing to the lack of approaches for surgeons to effectively distinguish PGs from surrounding thyroid glands (TGs) in the operation room. Herein, we report the development of biodegradable iron oxide nanoparticles (IONPs) as a promising contrast agent candidate for intraoperative PG visualization. We elucidated that locally administrated dark-colored IONPs readily diffuse in TGs but cannot infiltrate tissue-dense PGs, yielding a distinguishable contrast enhancement between PGs and TGs by naked eye observation. We performed unbiased and quantitative in vivo screenings to optimize particle size and concentration of IONPs for PG/TG contrast enhancement. Moreover, in vivo applications of IONPs via the local administration route demonstrate no adverse toxicities and can be biodegraded in the thyroid microenvironment within 3 months. To our knowledge, these promising findings provide the first in vivo evidence that IONPs can serve as a safe, biodegradable, and effective contrast agent candidate for improving PG visualization in thyroidectomy.

Development and validation of nomograms for predicting the risk probability of carbapenem resistance and 28-day all-cause mortality in gram-negative bacteremia among patients with hematological diseases.

Objectives: Gram-negative bacteria (GNB) bloodstream infections (BSIs) are the most widespread and serious complications in hospitalized patients with hematological diseases. The emergence and prevalence of carbapenem-resistant (CR) pathogens has developed into a considerable challenge in clinical practice. Currently, nomograms have been extensively applied in the field of medicine to facilitate clinical diagnosis and treatment. The purpose of this study was to explore risk indicators predicting mortality and carbapenem resistance in hematological (HM) patients with GNB BSI and to construct two nomograms to achieve personalized prediction. Methods: A single-center retrospective case-control study enrolled 244 hospitalized HM patients with GNB-BSI from January 2015 to December 2019. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis were conducted to select potential characteristic predictors of plotting nomograms. Subsequently, to evaluate the prediction performance of the models, the prediction models were internally validated using the bootstrap approach (resampling = 1000) and 10-fold cross validation. Results: Of all 244 eligible patients with BSI attributed to GNB in this study, 77 (31.6%) were resistant to carbapenems. The rate of carbapenem resistance exhibited a growing tendency year by year, from 20.4% in 2015 to 42.6% in 2019 (p = 0.004). The carbapenem resistance nomogram constructed with the parameters of hypoproteinemia, duration of neutropenia ≥ 6 days, previous exposure to carbapenems, and previous exposure to cephalosporin/ß-lactamase inhibitors indicated a favorable discrimination ability with a modified concordance index (C-index) of 0.788 and 0.781 in both the bootstrapping and 10-fold cross validation procedures. The 28-day all-cause mortality was 28.3% (68/240). The prognosis nomogram plotted with the variables of hypoproteinemia, septic shock, isolation of CR-GNB, and the incomplete remission status of underlying diseases showed a superior discriminative ability of poorer clinical prognosis. The modified C-index of the prognosis nomogram was 0.873 with bootstrapping and 0.887 with 10-fold cross validation. The decision curve analysis (DCA) for two nomogram models both demonstrated better clinical practicality. Conclusions: For clinicians, nomogram models were effective individualized risk prediction tools to facilitate the early identification of HM patients with GNB BSI at high risk of mortality and carbapenem resistance.

Antibacterial activity of chrysophsin-3 against oral pathogens and Streptococcus mutans biofilms.

Dental caries and pulpal diseases are common oral bacterial infectious diseases, the prevention and treatment of these diseases require the control of the causative pathogens, such as Streptococcus mutans (S. mutans) and Enterococcus faecalis. As a cationic antimicrobial peptide, Chrysophsin-3 has broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria which may cause a variety of oral infectious diseases. The present study evaluated the potential of chrysophsin-3 against several oral pathogens and S.mutans biofilms. The cytotoxic activity of chrysophsin-3 against human gingival fibroblasts (HGFs) was investigated for potential oral application. We use minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and time-kill assay to evaluate the killing effect of chrysophsin-3. Then scanning electron microscopy (SEM) and Transmission Electron Microscope (TEM) were used to analyze the change of morphology and membrane of the pathogens, Live/Dead staining and confocal scanning laser microscopy (CSLM) was used to observe S. mutans biofilms. The results indicate that chrysophsin-3 has varying antimicrobial activities against different oral bacteria. Chrysophsin-3 did not cause obvious cytotoxicity in HGFs at concentrations of 32-128 µg/ml for 5 min or 8 µg/ml for 60 min. SEM revealed membranous blebs and pore formation on the bacterial cell surface, and TEM showed loss of the nucleoid and dissolution of the cytoplasmic space. Furthermore, the CSLM images indicate that chrysophsin-3 can reduce the viability of the cells within the biofilms significantly and had a comparatively lethal effect against S. mutans biofilms. Taken together, our finding suggests that chrysophsin-3 has potential clinical application in oral infectious disease, especially in preventing and treating dental caries.