Multi-objective optimization via evolutionary algorithm (MOVEA) for high-definition transcranial electrical stimulation of the human brain.

Designing a transcranial electrical stimulation (tES) strategy requires considering multiple objectives, such as intensity in the target area, focality, stimulation depth, and avoidance zone. These objectives are often mutually exclusive. In this paper, we propose a general framework, called multi-objective optimization via evolutionary algorithm (MOVEA), which solves the non-convex optimization problem in designing tES strategies without a predefined direction. MOVEA enables simultaneous optimization of multiple targets through Pareto optimization, generating a Pareto front after a single run without manual weight adjustment and allowing easy expansion to more targets. This Pareto front consists of optimal solutions that meet various requirements while respecting trade-off relationships between conflicting objectives such as intensity and focality. MOVEA is versatile and suitable for both transcranial alternating current stimulation (tACS) and transcranial temporal interference stimulation (tTIS) based on high definition (HD) and two-pair systems. We comprehensively compared tACS and tTIS in terms of intensity, focality, and steerability for targets at different depths. Our findings reveal that tTIS enhances focality by reducing activated volume outside the target by 60%. HD-tTIS and HD-tDCS can achieve equivalent maximum intensities, surpassing those of two-pair tTIS, such as 0.51 V/m under HD-tACS/HD-tTIS and 0.42 V/m under two-pair tTIS for the motor area as a target. Analysis of variance in eight subjects highlights individual differences in both optimal stimulation policies and outcomes for tACS and tTIS, emphasizing the need for personalized stimulation protocols. These findings provide guidance for designing appropriate stimulation strategies for tACS and tTIS. MOVEA facilitates the optimization of tES based on specific objectives and constraints, advancing tTIS and tACS-based neuromodulation in understanding the causal relationship between brain regions and cognitive functions and treating diseases. The code for MOVEA is available at https://github.com/ncclabsustech/MOVEA.

The diagnostic value of blood sample NGS in patients with early periprosthetic joint infection after total hip arthroplasty.

The diagnostic value of next-generation sequencing (NGS) of blood samples from patients with periprosthetic joint infection (PJI) after total hip arthroplasty (THA) was evaluated by comparing it with drainage fluid NGS and bacterial culture. The study was designed as a retrospective diagnostic test. Thirty-six infected patients were diagnosed with PJI according to the Musculoskeletal Infection Society (MSIS) criteria and 57 volunteers were included in our study. NGS and bacterial culture were chosen to detect PJI after THA. Blood samples and drainage fluid were collected for NGS, and the drainage fluid, which was collected at the same time as the NGS drainage fluid sample, was used for bacterial culture. The primary outcomes of interest were sensitivity, specificity, and accuracy. In the infection group, 31 patients showed positive results by blood sample NGS, 33 patients showed positive results by drainage fluid NGS, and 17 patients showed positive bacterial culture results. In the control group, the results of 2 blood sample NGS, 16 drainage fluid NGS, and 3 bacterial cultures were positive. The sensitivity, specificity, and accuracy of the blood sample were 0.86, 0.96, and 0.92, respectively. The sensitivity, specificity, and accuracy of the drainage fluid samples were 0.92, 0.72, and 0.80, respectively. The sensitivity, specificity, and accuracy of bacterial culture were 0.47, 0.95, and 0.79, respectively. The study demonstrated that both the sensitivity and specificity of NGS were higher than those of bacterial culture, regardless of the kind of sample. Compared with drainage fluid NGS, the sensitivity of blood sample NGS was slightly lower (0.86 vs 0.92), but blood sample NGS showed higher specificity (0.96 vs 0.72). In total, the diagnostic value of blood sample NGS was superior to that of drainage fluid NGS and bacterial culture. The majority of infected patients could be identified by blood sample NGS. Moreover, because of its high specificity, blood sample NGS can not only detect infectious bacteria but also distinguish infectious from non-infectious bacteria, which is dramatically different from using drainage fluid NGS.

Retrospective Study from a Single Center to Identify Risk Factors Associated with Reinfection in Patients Undergoing 2-Stage Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND This study identified risk factors associated with reinfection and created a scoring system designed for patients with periprosthetic joint infection (PJI) who have undergone prosthetic resection and spacer implantation. MATERIAL AND METHODS Patients who underwent 2-stage revision for PJI from January 2010 to December 2017 were retrospectively analyzed in this study. Patients were divided into 2 groups: infection recurrence and infection cure. Demographic and clinical information, laboratory test results, and radiological images that were potentially associated with infection were obtained and analyzed. RESULTS Seven independent risk (protective) factors for infection recurrence in patients with PJI who underwent 2-stage hip revision surgery were identified: C-reactive protein level, type of bacterial infection, age, immunosuppression, albumin/globulin ratio, glucose level, and magnetic resonance imaging findings. Finally, a weighted scoring system of 100-mark system was established and the area under the curve was 0.965 (95% confidential interval=0.947-0.983). The predictive scores for low risk (≤30%), moderate risk (31-69%), and high risk (≥70%) of infection recurrence were ≤45, 46-77, and ≥78, respectively. CONCLUSIONS For patients with PJI who had already undergone joint resection and spacer implantation, this newly established scoring system might help determine the accurate risk of infection recurrence after a definitive new prosthesis implantation. Patients with scores greater than 78 points would be considered very likely to have an infection recurrence. Therefore, the second-stage revision surgery should be changed to an additional anti-infection treatment or a debridement surgery instead of a definitive prosthesis implantation surgery.

Clinical and radiologic outcomes in patients undergoing primary total hip arthroplasty with Collum Femoris Preserving stems: a comparison between the direct anterior approach and the posterior approach.

BACKGROUND: The direct anterior approach (DAA) and posterior approach (PA) are two of the most common surgical approaches used for total hip arthroplasty (THA) worldwide. The curved anatomical collum femoris-preserving (CFP) stem was designed to preserve the bone of the femoral neck and allow physiologic load transfer along the trabecular systems, which may better restore hip biomechanics, improve triplanar stem stability and improve the long-term survival rate. We believe this study will demonstrate whether the DAA is suitable for THA with CFP stems. METHODS: The data of patients who underwent primary THA with CFP stems from January 2010 to December 2015 were retrospectively analysed. These patients were divided into two groups (group A, DAA; group B, PA). The approach was selected by the surgeon. The demographic characteristics, preoperative diagnoses, preoperative Harris hip score, preoperative range of motion, postoperative complications, and radiologic measurements (neck-shaft angle, coronal alignment, sagittal alignment, stress shielding, anteversion, neck-preserving ratio, acetabular anteversion, acetabular inclination angle, acetabular depth, anterior-posterior offset, lateral offset, difference in leg length) were recorded for all patients. RESULTS: In this study, a total of 248 patients (185 male and 63 female) were included. No significant differences were found between group A and group B in terms of general patient information and radiologic measurements. However, the rate of nerve injury in group A (7/5.5%) was significantly higher than that in group B (1/0.8%) (p = 0.037). At 1 month after surgery, we found a significant difference between the two groups in the Harris hip score (HHS) (71.03 ± 8.04 in group A, 68.39 ± 8.37 in group B, P = 0.014) and forgotten joint score (FJS-12) (50.78 ± 7.57 in group A, 47.68 ± 7.34 in group B, P = 0.001). At 1 year after surgery, the mean FJS-12 score in group A (68.78 ± 7.54) was higher than that in group B (58.84 ± 8.91) (P < 0.001). At 5 years after surgery, the mean FJS-12 score in group A (73.38 ± 7.21) was higher than that in group B (67.16 ± 9.12) (P < 0.001). Post hoc analysis of the 1-month, 1-year, and 5-year postoperative FJS-12 scores using multiple linear regression analysis revealed that an excellent HHS led to good patient satisfaction at each time point. CONCLUSION: In summary, unlike a "standard" femoral stem, whose alignment might be affected by the surgical approach, alignment of the CFP stem is independent from the surgical approach. Even though the DAA had a higher nerve injury rate, nerve injury from the DAA did not typically cause severe dysfunction of the lower extremity. Therefore, decisions regarding the surgical approach for patients undergoing THA with CFP stems can be made primarily based on the preference of the surgeon.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Short uncemented femoral component for hip revision: prognosis and risk factors associated with failure.

BACKGROUND: The application of short femoral stems is partially restricted in revision surgery. This study will demonstrate the therapeutic effect and unsuitable situation for short stem revision. METHODS: Demographic characteristics of all patients were recorded in detail (Table 1). Anteroposterior view radiographic examinations of proximal femur are necessary before and after the operation for patients. The primary outcome of interest was the survival rate of the femoral stem at the final follow-up. Risk factors for failure were also investigated. The secondary outcomes of interest included the Harris hip score, excellent to good rate and incidence of complications. The Mann-Whitney U test was performed for comparisons between continuous variables. The chi-square test was performed for comparisons between categorical variables. Cox regression analysis was used to assess the association between potential risk factors and the failure of revision surgery. RESULTS: A total of 381 patients with short stems were retrospectively reviewed. There were 188 males and 193 females. The average age and body mass index before revision surgery were 58.85 ± 13.46 years and 23.72 ± 3.40 kg/m2, respectively. The mid-term survival rate of the short femoral component was 94.23%. The prognosis and complications of patients between the two groups were compared. There was no significant difference between the two groups in the Harris score, complication incidence or survival rate of the femoral component. The strongest risk factor in this study was intraoperative periprosthetic femoral fracture during revision surgery (HR = 5.477, 95% CI = 2.156-13.913). CONCLUSION: Three risk factors for failure were identified: ageing, osteoporosis and intraoperative periprosthetic femoral fracture during revision surgery. Therefore, a short femoral stem should be implanted in patients with these risk factors with additional caution.

Similarity Changes Analysis for Heart Rate Fluctuation Regularity as a New Screening Method for Congestive Heart Failure.

Congestive heart failure (CHF) is a chronic cardiovascular condition associated with dysfunction of the autonomic nervous system (ANS). Heart rate variability (HRV) has been widely used to assess ANS. This paper proposes a new HRV analysis method, which uses information-based similarity (IBS) transformation and fuzzy approximate entropy (fApEn) algorithm to obtain the fApEn_IBS index, which is used to observe the complexity of autonomic fluctuations in CHF within 24 h. We used 98 ECG records (54 health records and 44 CHF records) from the PhysioNet database. The fApEn_IBS index was statistically significant between the control and CHF groups (p < 0.001). Compared with the classical indices low-to-high frequency power ratio (LF/HF) and IBS, the fApEn_IBS index further utilizes the changes in the rhythm of heart rate (HR) fluctuations between RR intervals to fully extract relevant information between adjacent time intervals and significantly improves the performance of CHF screening. The CHF classification accuracy of fApEn_IBS was 84.69%, higher than LF/HF (77.55%) and IBS (83.67%). Moreover, the combination of IBS, fApEn_IBS, and LF/HF reached the highest CHF screening accuracy (98.98%) with the random forest (RF) classifier, indicating that the IBS and LF/HF had good complementarity. Therefore, fApEn_IBS effusively reflects the complexity of autonomic nerves in CHF and is a valuable CHF assessment tool.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Comparison of Bone Remodeling Between Collum Femoris-Preserving Stems and Ribbed Stems in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This study examined a cohort of patients who underwent bilateral THAs. CFP prostheses and ribbed prostheses were each used on both sides. We assessed the midterm clinical, radiological, and bone remodeling outcomes around prosthesis of these patients. MATERIAL AND METHODS From January 2009 to January 2013, 53 patients were enrolled in our study. We clinically evaluated all patients by recording Harris hip and Oxford hip scores. Some radiological indicators of the femoral prosthesis position were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean preoperative HHS of the CFP group and ribbed group were no significantly different (P=0.570). The neck-shaft angle in the ribbed group was significantly greater than in the CFP group (P<0.001). The CFP group had a greater offset (P<0.001). There was no significant difference in leg-length discrepancy (P=0.727) or Engh score between the 2 groups at the last follow-up (P=0.858). The preoperative BMD was increased at the last follow-up in Gruen zones 3 and 5 (P<0.05) and decreased in Gruen zones 1 and 7 (P<0.05) on the CFP side. BMD was increased in Gruen zone 4 (P=0.007) on the ribbed side. Pearson correlations and rate of complications were not significantly different. CONCLUSIONS Both the CFP and ribbed stem significantly improved the preoperative HHSs and OHSs. The bone remodeling of the CFP stem was more concentrated in the middle and distal regions of the prosthesis, while that of the ribbed stem was more concentrated in the proximal portion of the prosthesis.

Comparison of Clinical Outcomes, Radiological Outcomes and Bone Remodeling Outcomes Between Proximal Coated Single-Wedge New Stem and Full Coated Dual-Wedge Classic Stem in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This retrospective study investigated the clinical outcomes, radiological outcomes, and bone remodeling patterns associated with a Medial/Lateral Taper (M/L Taper) stem and Link Classic Uncemented (LCU) stem in 1-stage bilateral total hip arthroplasty (THA). MATERIAL AND METHODS The results of 52 patients who underwent 1-stage bilateral THA with a M/L Taper stem on one side and an LCU stem on the other between January 2012 and February 2015 were retrospectively compared. Patients were clinically assessed by the Harris hip score (HHS), visual analogue score (VAS) and incidence of complications. Radiological indicators were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean follow-up time was 5.2 years. At each follow-up, there was no difference in the HHS and VAS between the 2 groups. The neck-shaft angle, offset, vertical height of the rotational center and limb lengthening were lower in the M/L Taper group than in the LCU group (P<0.001). The Engh total score was lower in the LCU group (P=0.039). Significantly higher (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 1, 2, and 6. significantly lower (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 3 and 5. CONCLUSIONS Due to the increased postoperative neck-shaft angle, the full coated dual-wedge classic stem was prone to cause lower limb lengthening. The proximal coated single-wedge new stem patients were more likely to have an insufficient postoperative neck length. The new stem achieved load transfer and proximal fixation, leading to better proximal femoral bone preservation is more in line with human biomechanical characteristics.

Surgical treatment of thoracolumbar fracture with incomplete lower limb paralysis in a patient with COVID-19.

Since December 2019, COVID-19, an acute infectious disease, has gradually become a global threat. We report a case of thoracolumbar fractures (T12 and L1) and incomplete lower limb paralysis in a patient with COVID-19. After a series of conservative treatment which did not work at all, posterior open reduction and pedicle screw internal fixation of the thoracolumbar fracture were performed in Wuhan Union Hospital. Three weeks later, the patient could stand up and the pneumonia is almost cured. We successfully performed a surgery in a COVID-19 patient, and to our knowledge it is the first operation for a COVID-19 patient ever reported.

Influence of tumor extent on central lymph node metastasis in solitary papillary thyroid microcarcinomas: a retrospective study of 1092 patients.

BACKGROUND: The morbidity of papillary thyroid microcarcinomas is increasing worldwide. Surgery is the main treatment for papillary thyroid microcarcinomas, and the choice of surgical method partly depends on the T stage of the tumor. However, according to the American Joint Commission on Cancer staging system (7th edition), the T stage of papillary thyroid microcarcinomas with different tumor extent is unclear. We aimed to study the effect of tumor extent and other factors on central lymph node metastasis to explore the relationship between tumor extent and T stage and to identify the risk factors predicting central lymph node metastasis in papillary thyroid microcarcinomas. METHODS: We included 1092 patients diagnosed with solitary papillary thyroid microcarcinomas between July 2011 and April 2016. The tumor extent and other central lymph node metastasis risk factors were retrospectively analyzed. RESULTS: Univariate analysis revealed that capsule invasion and extracapsular extension (P = 0.013, <0.001; respectively) were significantly correlated with central lymph node metastasis. On multivariate analysis, extracapsular extension was independent central lymph node metastasis predictors (odds ratio 3.092, 95% CI 1.744-5.484), while capsule invasion was not (odds ratio 1.212, 95% CI 0.890-1.651). In addition, multivariate analysis revealed that male sex, tumor size >5 mm, and age <45 years were independent central lymph node metastasis predictors (odds ratio 2.072, 2.356, 2.302; 95% CI 1.483-2.894, 1.792-3.099, 1.748-3.031; respectively). CONCLUSIONS: This study supported that capsule invasion and tumor limited to the thyroid in papillary thyroid microcarcinomas were suitable for the lower T1, that is, capsule invasion in papillary thyroid microcarcinomas might not belong to the minimal extrathyroid extension included in T3 of TNM staging. In addition, patients with risk factors of extrathyroid extension, male sex, age <45 years, or tumor size >5 mm in papillary thyroid microcarcinomas should consider a more aggressive surgical treatment.

Diagnostic accuracy of ultrasonographic features for lymph node metastasis in papillary thyroid microcarcinoma: a single-center retrospective study.

BACKGROUND: Whether sonography is an appropriate imaging modality for cervical lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) remains unclear. Hence, this study aimed to evaluate the diagnostic value of ultrasonography (US) features for lymph node metastasis in PTMC. METHODS: Seven hundred twelve patients with PTMC who underwent conventional ultrasonography examinations of the cervical lymph nodes were included. All included cases underwent total thyroidectomy plus prophylactic central lymph node dissection. The included lymph nodes were marked superficially, and the corresponding lymph nodes were completely removed and sent for pathological examination. The US features of lymph nodes with and without metastasis were compared, and the odds ratios of the suspicious US features were determined with univariate and multivariate analyses. RESULTS: Round shape, loss of an echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were significantly more common in metastatic than nonmetastatic lymph nodes, whereas the boundary and echo did not significantly differ. Multivariate logistic regression analysis showed that round shape, loss of echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were independent predictive factors for the assessment of metastatic lymph nodes. Round shape had the highest sensitivity of all variables, while loss of an echogenic fatty hilum had the highest specificity and accuracy. The area under the receiver operating characteristic curve, which was calculated to verify the relationship between the various US features and metastatic lymph nodes, was 0.793. CONCLUSIONS: Our study found that the US features of round shape, cystic change, calcification, loss of echogenic fatty hilum, and abnormal vascularity were useful sonographic criteria for differentiating between cervical lymph nodes with and without metastasis.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

Laser induced mechanisms controlling the size distribution of metallic nanoparticles.

This paper describes a model to simulate changes in the size distribution of metallic nanoparticles (NPs) in TiO2 films upon continuous wave light excitation. Interrelated laser induced physical and chemical processes initiated directly by photon absorption or by plasmon induced thermal heating are considered. Namely the model takes into account the NP coalescence, Ostwald ripening, the reduction of silver ions and the oxidation of metallic NPs, competitive mechanisms that can lead to counter-intuitive behaviors depending on the exposure conditions. Theoretical predictions are compared successfully to the experimental results deduced from a thorough analysis of scanning transmission electron microscopy (STEM) pictures of Ag:TiO2 films processed with a scanning visible laser beam at different speeds. Ag:TiO2 systems are considered for many applications in solar energy conversion, photocatalysis or secured data printing. Numerical investigations of such a system provide a better understanding of light induced growth and shrinking processes and open up prospects for designing more efficient photocatalytic devices based on metal NP doped TiO2 or for improving the size homogeneity in self-organized metallic NP patterns, for instance.

Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis.

BACKGROUND: The objective of this study is to perform a meta-analysis to evaluate the associations between the BRAF(V600E) mutation status and aggressive clinicopathological features and poor prognostic factors in papillary thyroid cancer. METHODS: A literature search was performed within the PubMed, MEDLINE, Web of Science databases, and EMBASE databases using the Medical Subject Headings and keywords from January 2003 to July 2015. Individual study-specific odds ratios and confidence intervals were calculated, as were the Mantel-Haenszel pooled odds ratios for the combined studies. RESULTS: Sixty-three studies of 20,764 patients were included in the final analysis. Compared with wild-type BRAF, the BRAF(V600E) mutation was associated with aggressive clinicopathological factors, including extrathyroidal extension, higher TNM stage, lymph node metastasis, and recurrence, and was associated with reduced overall survival; however, there was no significant association between the presence of BRAF mutation and distant metastasis. CONCLUSIONS: BRAF mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in papillary thyroid cancer. Accordingly, aggressive treatment should be considered for papillary thyroid cancer patients with BRAF mutation.

Clinical efficacy and safety of composite non-cross-linked hyaluronic acid for treating tear trough-lower eyelid bag deformity.

BACKGROUND: Tear trough-eye bag deformities may appear in young Asian patients due to the weak support of their facial skeletons. For these patients with better periorbital skin elasticity, the injection may be more suitable than surgery for treating tear trough-lower eyelid bag deformity. AIMS: Identify the clinical efficacy and safety of non-cross-linked HA in the treatment of tear trough-lower eyelid bag deformity. METHODS: In this study, we analyzed pre- and postinjection photographs of 55 patients treated with non-cross-linked hyaluronic acid (HA) for tear trough-lower eyelid bag deformity. RESULTS: The mean [SD] scores of modified Goldberg score suggested that the most significant improvement of preoperative and postoperative scores was in tear trough depression, followed by infraorbital triangular depression, orbital fat prolapse, loss of skin elasticity, and skin transparency. Only transient localized complications were observed, including bruising, swelling, and erythema. There were no serious complications, such as skin necrosis or visual impairment. CONCLUSIONS: Our study confirmed the beneficial efficacy and minor complications of composite non-cross-linked HA for the treatment of tear trough-lower eyelid bag deformity.

Bionic aggregation-induced emission photosensitizer for enhanced cancer immunotherapy.

Cold exposure therapy (CE), as an inexpensive method, has shown great potential in cancer therapy. Exploring the combined anti-tumor mechanism of CE and traditional therapies (such as photodynamic therapy (PDT)) is exciting and promising. Here, a bionic aggregation-induced emission photosensitizer system (named THL) is designed for combined CE to enhance anti-tumor immunotherapy. THL inherits the homologous targeting ability of tumor derived exosomes, promoting the enrichment of THL at the tumor site. Under external illumination, THL generates hydroxyl radicals and superoxide anions through type I PDT. In addition, mice are pretreated with cold exposure, which promotes THL mediated PDT and reactive oxygen species (ROS) generation by reducing the production of ATP and GSH in tumor tissue. This combination therapy increases production of ROS within the tumor, inhibits the growth of distant tumors, recurrent and rechallenged tumors and increases the number of cytotoxic CD8+T cells and memory T cells. Compared to PDT alone, combination therapy shows greater advantages in tumor immunotherapy. The combination therapy strategy provides new ideas for cancer immunotherapy.

Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing.

Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care.

MicroRNAs Associated with Keloids Identified by Microarray Analysis and In Vitro Experiments.

MicroRNAs (miRNAs) play a crucial role in gene regulation and the development of keloid. This research aimed to identify and verify miRNAs associated with keloids by microarray analysis and in vitro experiments, shedding light on seeking for potential therapeutic molecular targets. In this study, the weighted gene co-expression network analysis was performed based on the GSE113620. The key miRNA module most relevant to the keloid was further screened to identify hub miRNAs, and then hub miRNAs was verified by the microarray analysis and qRT-PCR experiments. Additionally, targeted genes of hub miRNAs were predicted and verified. Gene ontology (GO) analysis and KEGG enrichment analysis were also conducted. Five miRNA modules were divided, and the blue module exhibited the highest correlation with keloids. Then, hsa-miR-127-3p, hsa-miR-214-3p, hsa-miR-155-5p, hsa-miR-409-5p, and hsa-miR-542-5p were identified as the hub miRNAs. Subsequently, the microarray analysis and qRT-PCR results demonstrated that the expression of five miRNAs were upregulated in keloid tissues. The GO analysis revealed that the target genes of these miRNAs were mainly enriched in biological processes including gene transcription, protein phosphorylation and the MAPK (mitogen-activated protein kinase) cascade, and the KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway were significantly enriched. In conclusion, these five miRNAs (hsa-miR-127-3p, hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-409-5p, and hsa-miR-542-5p) play vital roles in the pathogenesis of keloid and might be potential therapeutic targets. These miRNAs might regulate genes enriched in gene transcription, protein phosphorylation, the MAPK cascade, and the PI3K-Akt signaling pathway.