Search

Background: Congenital pseudarthrosis of the tibia (CPT) is a dominant health challenge in pediatric orthopedics. The essential process in the development of CPT is the limited capacity of mesenchymal stem cells (MSCs) derived from CPT to undergo osteogenic differentiation. Our research aimed to elucidate the role and mechanism of methyltransferase-like 3 (METTL3) in the osteogenic differentiation process of CPT MSCs. Methods: The osteogenic differentiation medium was used to culture MSCs, and the detection of osteogenic differentiation was performed using Alizarin Red S and alkaline phosphatase (ALP) assays. Gene or protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, or immunofluorescence (IF) staining. The m6A modification of Homeobox D8 (HOXD8) was verified by methylated RNA immunoprecipitation (MeRIP) assay. Interactions between METTL3 and HOXD8 or HOXD8 and integrin alpha 5 (ITGA5) promoter were validated by the luciferase reporter gene, RIP, and chromatin immunoprecipitation (ChIP) assays. Results: METTL3 overexpression enhanced CPT MSCs' osteogenic differentiation. METTL3 stabilized the HOXD8 in an m6A-dependent manner. Moreover, the overexpressed ITGA5 up-regulated the CPT MSCs’ osteogenic differentiation. Further, HOXD8 could transcriptionally activate ITGA5. METTL3 increased the transcription of ITGA5 via HOXD8 to enhance the osteogenic differentiation of CPT MSCs. Conclusion: METTL3 promoted osteogenic differentiation via modulating the HOXD8/ITGA5 axis in CPT MSCs.

Abstract Background When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture Purpose To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children Methods From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. Exclusion criteria: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated Results It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years Conclusion Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research

Abstract Purpose To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. Methods A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). Results Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P

Background: The role of body mass index (BMI) in basal cell carcinoma (BCC) risk remains controversial, and limited information is available regarding the relationship between other physical measurements and BCC. Several recent studies have found a positive effect of adiposity on improved survival when obesity was determined solely by BMI (the ''obesity paradox''). We hypothesize that body fat percentage (BFP) may serve as a more sensitive risk factor for BCC than BMI. Methods: The study conducted a retrospective analysis of clinical data from two distinct centers in China. Individual patient-level data were obtained from medical record reviews spanning January 1, 2015, to December 31, 2022. Associations with outcomes were analyzed using univariate and stratified analyses and assessed using multiple logistic regression with adjustment for confounding factors. Additionally, we performed a meta-analysis to further test the observations in our study. Results: A total of 337 patients, ranging in age from 50 to 91 years, with a mean age of 66.88 (standard deviation 10.16), were included. We observed no significant association between BMI and BCC after adjusting for confounders (OR: 0.71, 95 % CI: 0.36–1.40, P = 0.3186). There was also no convincing effect in a meta-analysis (n = 158,741) (OR: 0.99, 95 % CI: 0.93–1.06, P = 0.8). Furthermore, BFP was found to be associated with BCC (OR: 2.64, 95 % CI: 1.17–5.97, P = 0.0196), supported by strong clinical evidence. Conclusions: Our study supports the hypothesis that BFP is superior to BMI in assessing BCC risk. Multiple logistic regression analyses, coupled with meta-analysis, provided robust evidence that BFP is a sensitive risk factor for BCC, while BMI appears unrelated to risk. According to these findings, routine healthcare practices could benefit from utilizing BFP measurements. The reduction of body fat percentage in low-fat diets may be beneficial for adjuvant treatment of BCC.

Abstract In this research, a modeling approach of rainfall generator coupled with high resolution rainfall products were proposed to generate designed rainfall events under multiple spatial and temporal distributions, which was then employed to analyze the impacts of spatial and temporal rainfall heterogeneities on peak runoff for watersheds. Three scenarios were developed under multiple degrees of impermeable underlying surface areas within an urban watershed in south China. Detailed runoff processes were analyzed through the adoption of a distributed hydrological model (GSSHA). A covariance analysis method combined with rainfall spatio‐temporal heterogeneity characteristic were used to quantify heterogeneity effects on peak runoff. Results indicated that coupling short period (2008–2016) remotely rainfall data and RainyDay results could successfully reproduce designed rainfall events, spatio‐temporal heterogeneity of rainfall contributed significantly to the peak runoff, which was greater than those by rainfall duration and capacity, and the increase in impermeable underlying surface enhanced the complexities of the effects. Over each rainfall duration with increasing rainfall return period, the indicator of rainfall peak coefficient (RWD) would decrease and then increase. Regarding the total rainfall center (tg), 25 mm/h threshold rainfall spatial coverage (A25) decreased with increasing imperviousness, 1‐h maximum rainfall (Rmax) surged with increasing imperviousness at rainfall duration of 2 and 24 h. Innovations of this research lied in: combination of a rainfall generator model based on a stochastic storm transposition technique and remote‐sensing rainfall data to generate designed rainfall events, a rainfall spatial and temporal heterogeneities index system was developed to reveal how the changing characteristics of rainfall distribution and the impacts on peak runoff, and in‐depth analysis of the impacts on runoff peak under multiple urban development scenarios for increasing capability in flood control/prevention.

The intersection of computer science and art has sparked a wave of innovation, particularly in digital visualizations and interactive installations. This abstract explores the symbiotic relationship between these disciplines, highlighting groundbreaking advancements and creative endeavors. Innovations in digital visualizations leverage algorithms and computational techniques to transform data into visually engaging representations. From intricate data sculptures to immersive virtual reality experiences, computer scientists and artists collaborate to push the boundaries of storytelling and communication. These visualizations not only convey complex information effectively but also evoke emotional responses, bridging the gap between technology and human perception. Interactive installations blur the lines between audience and artwork, inviting participation and engagement. Through sensors, augmented reality, and responsive environments, users become active participants in the creation of art, shaping and influencing their experiences in real-time. This dynamic interaction fosters new forms of expression and challenges traditional notions of artistic production. By exploring the intersection of computer science and art, this abstract underscores the transformative power of interdisciplinary collaboration. Through experimentation, exploration, and innovation, digital visualizations and interactive installations continue to redefine the possibilities of creative expression in the digital age.

Abstract HEI10 is a conserved E3 ubiquitin ligase involved in crossover formation during meiosis, and is thus essential for both male and female gamete development. Here, we have discovered a novel allele of HEI10 in rice that produces a truncated HEI10 protein missing its N-terminal RING domain, namely sh1 (shorter hei10 1). Unlike previously reported hei10 null alleles that are completely sterile, sh1 exhibits complete male sterility but retains partial female fertility. The causative sh1 mutation is a 76 kb inversion between OsFYVE4 and HEI10, which breaks the integrity of both genes. Allelic tests and complementation assays revealed that the gamete developmental defects of sh1 were caused by disruption of HEI10. Further studies demonstrated that short HEI10 can correctly localise to the nucleus, where it could interact with other proteins that direct meiosis; expressing short HEI10 in hei10 null lines partially restores female fertility. Our data reveal an intriguing mutant allele of HEI10 with differential effects on male and female fertility, providing a new tool to explore similarities and differences between male and female meiosis.

A dual-linearly polarized (DLP) magneto-electric (ME) dipole antenna is proposed for the in-band full-duplex (IBFD) application. It is formed by ME dipoles with a shared central part, giving a compact and symmetrical antenna structure. It has four isolated channels, two for dual-LP transmitting (TX) and the other two for dual-LP receiving (RX). Due to the symmetrical structure, it can provide similar radiation patterns for both the TX and RX ports. Good isolation between any two of all four ports is obtained over a wide frequency range by modifying the antenna structure without introducing any additional complex feeding structures. To validate the proposed antenna, a prototype was fabricated and measured. The measured isolation of any two of four ports is better than 20.9 dB over the wide operating frequency band from 1.90 to 2.75 GHz (36.6%). The measured realised gain in the broadside direction and the measured radiation pattern remain stable in the whole operating frequency band and are similar for the different ports.

To address global phosphorus reduction challenges, we establish a quantitative framework for anthropogenic phosphorus emissions using a lifecycle model and decomposition analysis. Focusing on China's Pearl River Delta urban agglomeration, we highlight persistent difficulties in controlling phosphorus emissions from agricultural fertilizers and the emerging issue from industrial products. Emission intensity is a crucial factor for phosphorus reduction, yet gradually offset by affluence and population growth. Prioritizing agricultural control with supplementary industrial reduction, we delve into the decoupling challenge between phosphorus emissions, population expansion, and economic development. Proposing green economic development, our approach contributes to achieving sustainable phosphorus management goals.

Summary: Cardiac dysfunction, an early complication of endotoxemia, is the major cause of death in intensive care units. No specific therapy is available at present for this cardiac dysfunction. Here, we show that the N-terminal gasdermin D (GSDMD-N) initiates mitochondrial apoptotic pore and cardiac dysfunction by directly interacting with cardiolipin oxidized by complex II-generated reactive oxygen species (ROS) during endotoxemia. Caspase-4/11 initiates GSDMD-N pores that are subsequently amplified by the upregulation and activation of NLRP3 inflammation through further generation of ROS. GSDMD-N pores form prior to BAX and VDAC1 apoptotic pores and further incorporate into BAX and VDAC1 oligomers within mitochondria membranes to exacerbate the apoptotic process. Our findings identify oxidized cardiolipin as the definitive target of GSDMD-N in mitochondria of cardiomyocytes during endotoxin-induced myocardial dysfunction (EIMD), and modulation of cardiolipin oxidation could be a therapeutic target early in the disease process to prevent EIMD.

ObjectivesThis study aimed to explore the current status and trends of acupuncture for neurodegenerative diseases (NDs) in the last decade and provide new insights for researchers in future studies.MethodsThe publications concerning acupuncture treatment for NDs published between 2014 and 2023 were extracted from the Web of Science Core Collection. We used CiteSpace and VOSviewer to analyze data on numbers of annual publications, countries, institutions, cited journals, cited authors, cited references, keywords, and citation bursts about acupuncture for NDs.ResultsA total of 635 publications were obtained from 2014 to 2023. We identified the most prolific journals, countries, institutions, authors, patterns of authorship, and the main direction of future research in the field of acupuncture for NDs in the last decade. The country, institution, and journal with the most publications are China (389 articles), Beijing University of Chinese Medicine (56 articles), and Evidence Based Complementary and Alternative Medicine (42 articles), respectively. The high-frequency keywords focused on “Alzheimer's disease,” “Parkinson's disease,” “acupuncture,” “dementia,” and “electroacupuncture.” The top five keywords in terms of centrality were “cerebral ischemia,” “acupuncture stimulation,” “fMRI,” “apoptosis,” and “deep brain stimulation.”ConclusionThe results from this bibliometric study provide insight into the research trends in acupuncture therapy for NDs, and the current status and trends of the past decade, which may help researchers confirm the current status, hotspots, and frontier trends in this field.

Skin damage resulting from burns, injuries, or diseases can lead to significant functional and esthetic deficits. However, traditional treatments, such as skin grafting, have limitations including limited donor skin availability, poor aesthetics, and functional impairment. Skin tissue engineering provides a promising alternative, with engineered artificial skins offering a highly viable avenue. Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments, particularly for severe burns, chronic wounds, and other skin injuries or defects. These artificial skins aim to promote wound healing, provide temporary coverage, permanent skin replacement, and restore the skin's barrier function. Artificial skins have diverse applications in medicine and wound care, addressing burns, chronic wounds, and traumatic injuries. They also serve as valuable tools for research in tissue engineering, offering experimental models for studying wound healing mechanisms, testing new biomaterials, and exploring innovative approaches to skin regeneration. This review provides an overview of current construction strategies for engineered artificial skin, including cell sources, biomaterials, and construction techniques. It further explores the primary application areas and future prospects of artificial skin, highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.

AbstractContext Diabetic wounds (DW) are a complication of diabetes and slow wound healing is the main manifestation. Methylene blue (MB) has been shown to exhibit therapeutic effects on diabetes-related diseases.Objective To investigate the mechanisms of action of MB-nanoemulsion (NE) in the treatment of DW.Materials and methods The concentration of MB-NE used in the in vivo and in vitro experiments was 0.1 mg/mL. Streptozocin-induced diabetic mice were used as models. The mice were separated into nondiabetic, diabetic, MB-NE treated, and NE-treated groups. Intervention of high glucose-induced human umbilical vein endothelial cells using MB-NE. The mechanism by which MB-NE promotes DW healing is investigated by combining histological analysis, immunofluorescence analysis, TUNEL and ROS assays and western blotting.Results In diabetic mice, the MB-NE accelerated DW healing (p

Abstract During the process of wound healing, fibroblasts migrate to the wound site and perform essential functions in promoting cell proliferation, as well as synthesizing and secreting the extracellular matrix (ECM). However, in diabetic wounds, senescent fibroblasts exhibit impaired proliferative capacity and fail to synthesize essential ECM components. Pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme regulating energy metabolism, has been implicated in modulating cellular senescence and fibroblast function. However, its specific role in diabetic wounds remains poorly understood. In this study, we conducted a series of in vivo and in vitro experiments using STZ-induced diabetic mice and human dermal fibroblasts. We evaluated cellular senescence markers, including SA-β-gal, P53, P16, P21, and PAI-1, as well as senescence-associated secretory phenotype (SASP) factors. Finally, we observed that PDK4 increased in normal wound healing, but its expression was insufficient in diabetic wounds. Significantly, the overexpression of PDK4 demonstrated the potential to accelerate diabetic wound healing and improve the senescence phenotype both in vivo and in vitro. Furthermore, our study elucidated the underlying mechanism by which PDK4 improved the senescent phenotype through the enhancement of glycolysis and regulation of YAP and JNK pathway. The effect was dependent on metabolic reprogramming and subsequent reduction of reactive oxygen species (ROS), which was mediated by PDK4. Overall, our findings highlight the potential of PDK4 as a promising therapeutic target for addressing diabetic wounds.

ObjectiveThe aim of this study is to summarize and demonstrate the different sterilization methods and surgical techniques for open fractures with impacted bone segments in the lower limbs.MethodsA retrospective analysis was conducted on the clinical characteristics, treatment methods, and outcomes of a case involving a 10.5 cm extruded segment of the femur in a 9-year-old male with a right femoral comminuted fracture treated at our center. Additionally, a retrospective review and summary were conducted on all reported cases of open fractures with impacted bone segments in the lower limbs.ResultsOur center treated a 9-year and 11-month-old male child who presented with a Gustilo type IIIB open fracture of the femur along with a large segment of the femur being ejected as a result of a car accident. The child was resuscitated to correct hypovolemic shock, underwent emergency wound debridement, and had Ilizarov external fixation of the femur. The ejected femur segment was sterilized using ethylene oxide and re-implanted four days after the injury. A literature review showed that out of the cases of open fractures with impacted bone segments in the lower limbs, there were 14 cases involving the femur and 5 cases involving the tibia. Among them, sterilization was performed using povidone-iodine in 6 cases, high-pressure steam sterilization in 3 cases, and other methods including gamma-ray irradiation and soaking in antibacterial solution were used in the remaining cases. In terms of surgical methods, 7 cases were fixed with locking plates, 3 cases were fixed with external fixation devices, 1 case was immobilized in a cast, 1 case was fixed with an intramedullary rod, and 4 cases involved a combination of external fixation and internal fixation. The average time for re-implantation was 7.6 days after the injury. There were no serious complications such as infection or non-union observed in any of the cases during follow-up.ConclusionEthylene oxide can be considered a reliable choice for the reimplantation of displaced bone segments in open fractures after sterilization.

Treating anaerobic digestion (AD) slurry as industrial wastewater not only consumes a significant amount of energy but also wastes its inherent abundant nutrients, particularly the high ammonium content. Ammonia recovery from AD slurry has attracted attention in recent years and biochar has tentatively been used to adsorb ammonia nitrogen. However, most of the previous studies used pure ammonium chloride solution to simulate ammonia-rich wastewater and ignored the influence of other components. Furthermore, how the physico-chemical properties of biochar influence the adsorption performance of ammonia in AD slurry remains unknown. Therefore, this study focused on the investigation of the adsorption behavior of different types of biochar to ammonia nitrogen in AD slurry. Biochar generated from rice straw, coconut shell, and wood shaving under pyrolysis temperatures of 300 °C, 500 °C, and 700 °C were used to adsorb ammonia from food waste (FW) AD slurry, and five different particle sizes of biochar were also tested. The results showed that biochar derived from rice straw (up to 9.44 mg/g) and coconut shell (up to 8.86 mg/g) had higher ammonium adsorption capacity than biochar derived from wood shaving (up to 5.13 mg/g). Moreover, low pyrolysis temperature resulted in high adsorption capacity, while particle size and surface area of the biochar were not the critical factors determining the adsorption capacity. The correlation results demonstrated that the H/C (aromaticity), O/C (hydrophilicity), pH, electrical conductivity (EC), and ash content influenced the adsorption significantly. Based on the kinetics model results, it seems that physical adsorption was the main adsorption mechanism, while ion exchange and reaction with function groups also contributed to the adsorption. Moreover, the lower adsorption capacity was observed in this study where the real FW AD slurry was used as compared to other studies where pure ammonium chloride solution was used, which implied that microorganisms in FW AD slurry may colonize on the surface or pores of biochar, resulting in a negative effect on the adsorption capacity of biochar. The results derived from this study provided technical support for ammonia recovery of AD slurry.

Stormwater pipeline is an essential pathway to transfer stormwater runoff into nearby receiving water bodies. Understanding the composition, co-occurrence patterns, and function of the microbial communities in stormwater pipeline sediments can help to provide management and control strategies for stormwater runoff pollution to safeguard water safety and ecological health of the urban water environment. This study employs 16S rRNA gene amplicon sequencing to probe the microbial communities in stormwater pipeline sediments of a highly urbanized area in Guangzhou, China. Results show that the sediment bacterial community is rich in Listeria, Prevotella, Stenotrophomonas, and Pseudomonas, which all pertain to pathogens. Methanogens (Methanobacterium, Methanosaeta, Methanosarcina, and Methanobrevibacter) and ammonia-oxidizing archaea (Ca. Nitrosopelagicus, Ca. Nitrososphaera, and Ca. Nitrosotenuis) dominated the archaeal community in stormwater pipeline sediments. These microbial functions are further validated by the function prediction of the overall microbial community. The co-occurrence network and microbe-environment correlation analyses suggest that particulate C-N-P components play a more crucial role, in comparison to dissolved ones in regulating the sediment microbiome, although not all samples follow this mechanism. These findings are expected to contribute to the pollution control of stormwater runoff in stormwater pipeline systems and provide valuable guidance for improving the environmental well-being of urban water ecosystems.

ObjectiveFatal road accidents are statistically rare, posing challenges for accurate estimation through the classic logit model (LM). This study seeks to validate the efficacy of a rare events logistic model (RELM) in enhancing the precision of fatal crash estimations.MethodsBoth LM and RELM were employed to examine the relationship between pertinent risk factors and the incidence of fatal crashes. Crash-injury datasets sourced from Hillsborough County, Florida served as the empirical basis for evaluating the performance metrics of both LM and RELM.ResultsThe analysis revealed that RELM yielded more accurate predictions of fatal crashes compared to LM. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) for each model was computed to offer a comparative performance assessment. The empirical evidence notably favored RELM over LM as substantiated by superior AUC values.ConclusionThe study offers empirical validation that RELM is demonstrably more proficient in predicting fatal crashes than the LM, thereby recommending its application for nuanced traffic safety analytics.

Abstract Background and Objectives Surgery is an essential treatment for non‐distant metastatic cutaneous melanoma (NMCM). We aim to construct and validate prognostic nomograms based on surgical approaches and the clinicopathological characteristics of NMCM patients. Methods Data of patients diagnosed with cutaneous melanoma from 2004 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Two online nomograms were constructed to predict the 3, 5‐year melanoma‐specific survival (MSS) for NMCM patients based on the surgical approaches. These nomograms were evaluated by the dynamic Harrell's concordance index (C‐index), decision curve analysis and clinical impact curve. Both internal and external data verification were conducted. Results A total of 14,091 NMCM cases were included in this study. The C‐index of the nomograms for the excisional surgery group and amputation group were 0.818 and 0.806, respectively, and 0.763 and 0.731, respectively, in our hospital data validation. After internal and bootstrap verification, our two nomograms showed good accuracy and practicality. Conclusion NMCM patients exhibited equal survival rates independent of resection margin size, while those who needed amputation had worse survival rates. We generated two online nomograms distinguished by surgical approach to predict NMCM patient survival based on clinicopathological characteristics.

Abstract A novel newsvendor model-based framework for regional industrial water resources allocation that considers uncertainties in water supply and demand was proposed in this study. This framework generates optimal water allocation schemes while minimizing total costs. The total cost of water allocation consists of the allocated water cost, the opportunity loss for not meeting water demand, and the loss of the penalty for exceeding water demand. The uncertainties in water demand and supply are expressed by cumulative distribution functions. The optimal water allocation for each water use sector is determined by the water price, the unit loss of the penalty and opportunity loss, and the cumulative distribution functions. The model was then applied to monthly water allocation for domestic, industrial, and agricultural water use in two counties of Huizhou City, China, whose water supply mainly depends on Baipenzhu Reservoir. The water demand for each water use sector and the monthly reservoir inflow showed good fits with the uniform and P-III distributions, respectively. The water demand satisfied ratio for each water use sector was stable and increased for the optimal water allocation scheme from the newsvendor model-based framework, and the costs were lower compared with the actual water allocation scheme. The novel framework is characterized by less severe water shortages, lower costs, and greater similarity to actual water use compared with the traditional deterministic multi-objective analysis model, and demonstrates strong robustness in the advantages of lower released surplus water and higher water demand satisfied ratio. This novel framework yields the optimal water allocation for each water use sector by integrating the properties of the market (i.e., determining the opportunity loss for not meeting water demand) with the government (i.e., determining the water price and the loss of the penalty for exceeding water demand) under the strictest water resources management systems.

Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades, while their short in vivo residence, alloimmune reactions, undesired behaviors, and dramatic losses of cell functions still hinder the translation of them into clinic. Here, inspired by the natural components of stem cell niches, we presented novel microfluidic hydrogel microcarriers with extracellular matrix (ECM)-like composition and adipose-derived stem cells (ADSCs) encapsulation for diabetic wound healing. As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl (HAMA) onto the Fibronectin (FN) molecule chain (FN-HAMA), the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities. Based on these features, we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization, follicular rejuvenation, and collagen deposition in a mouse diabetic wound model. These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.

Abstract Objectives To investigate the clinical efficacy and safety of open reduction through anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip. Method A total of 23 patients (25 hips) less than 2 years with developmental dysplasia of the hip treated by open reduction through anterior minimally invasive approach were treated in our hospital from August 2016 to March 2019. Through the anterior minimally invasive approach, we enter from the gap between sartorius muscle and tensor fasciae lata without cutting off rectus femoris muscle, which can effectively expose the joint capsule and reduce the damage to medial blood vessels and nerves. The operation time, incision length, intraoperative bleeding, hospital stay and surgical complications were observed. The progression of developmental dysplasia of the hip and avascular necrosis of the femoral head were evaluated by imaging examination. Result All patients were performed with follow-up visit for an average of 22 months. The average incision length was 2.5 cm, the average operation time was 26 min, the average intraoperative bleeding was 12ml, and the average hospital stay was 4.9 days. All patients received concentric reduction immediately after operation, and no re-dislocation occurred. At the last follow-up visit, the acetabular index was (25.8 ± 6.4°). During the follow-up visit, X-ray showed avascular necrosis of the femoral head in 4 hips (16%). Conclusion open reduction through anterior minimally invasive approach can achieve good clinical effect in the treatment of infantile developmental dysplasia of the hip.

AbstractBackground Resveratrol (RSV) that possesses anti-oxidative, anti-inflammatory, and pro-angiogenic effects is an effective drug for diabetic wound (DW), while its pharmacological mechanism remains to be elucidated. In this study, we apply network pharmacology and experimental validation approach to reveal the potential mechanism of RSV against DW.Methods We obtained potential targets for RSV and DW from the publicly available database. Using interaction networks and conducting GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to explore the relationship between RSV and DW. To validate the pharmacological mechanism of RSV, we induced the DW model.Results Ninety overlapped targets between RSV and DW were obtained, and the hub genes of the PPI network included TNF, IL-6, CASP3, MAPK3, VEGFA, IL-1β, AKT1, and JUN. Based on target-pathway networks, the AGE-RAGE signalling pathway was involved in the RSV treatment of DW. Furthermore, in vivo experiments revealed that RSV significantly promoted wound healing in diabetic mice and attenuated the expression of pro-inflammatory cytokines in wound tissue. Meanwhile, RSV could inhibit the AGE-RAGE signalling pathway and thus reduce the activation of NF-κB.Conclusion This study initially revealed the biological mechanism of RSV for treating DW through multi-target and multi-pathway. AGE-RAGE, FoxO, MAPK, PI3K-AKT and other signalling pathways may be the main pathways of RSV in treating DW. RSV reduces the inflammatory response by inhibiting the AGE-RAGE signalling pathway, which in turn promotes DW healing.

Malignant melanoma is a highly aggressive tumor, and lymph node metastasis significantly impacts the prognosis and treatment of this condition. Sentinel node biopsy, as a less invasive alternative to traditional dissection, offers convenience, safety, and improved efficiency in assessing local lymph node status. It provides valuable staging information and aids in determining appropriate follow-up treatment. The evolution and enhancement of technical and conceptual aspects associated with sentinel node biopsy have transformed the management of malignant melanoma. Notably, several large multicenter trials have challenged the necessity of complete lymph node dissection, leading to a paradigm shift. While some controversy remains, the standard of care for melanoma is progressing toward a consensus.

Background This study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical treatment.Method The children with CPT who were treated at our institution between 1 January 2013 and 31 December 2020 were retrospectively reviewed. The independent variable was preoperative concurrent fibular pseudarthrosis, and the dependent variable was postoperative ankle valgus. Multivariable logistic regression analysis was performed after adjusting for variables that might affect the risk of ankle valgus. Subgroup analyses with stratified multivariable logistic regression models were used to assess this association.Results Of the 319 children who underwent successful surgical treatment, 140 (43.89%) developed ankle valgus deformity. Moreover, 104 (50.24%) of 207 patients with preoperative concurrent fibular pseudarthrosis developed an ankle valgus deformity compared with 36 (32.14%) of 112 patients without preoperative concurrent fibular pseudarthrosis (p=0.002). After adjusting for sex, body mass index, fracture age, age of patient undergoing surgery, surgery method, type 1 neurofibromatosis (NF-1), limb-length discrepancy (LLD), CPT location and fibular cystic change, patients with concurrent fibular pseudarthrosis presented a higher risk of ankle valgus than those without concurrent fibular pseudarthrosis (OR 2.326, 95% CI 1.345 to 4.022). This risk further increased with CPT location at the distal one-third of the tibia (OR 2.195, 95% CI 1.154 to 4.175), age

In rivers, riverbeds are considered to have dual properties as a short-term sink and a source of further mobilization for microplastics. To better understand the sources, storage, and fate of microplastics in river systems, this study quantified the formation of microplastic hotspots in riverbeds and seasonal variations in microplastic inventories in riverbeds, especially for small-sized microplastics (

Summary: Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

BackgroundPhyseal bar resection has been used for partial growth arrest treatment for a decade while removing the bony bar minimally invasively and accurately is challenging. This research aims to illustrate a modified arthroscopically assisted surgery, by which all the procedure was under all-inside visualization, without the constant exchange between burring under fluoroscopy, followed by irrigation, suction, and arthroscopy of the canal.MethodsWe retrospectively reviewed the patients who sustained physeal bar resection under direct all-inside visualization of the arthroscope during 2016–2021. Patients who underwent physeal bar resection with the aid of an arthroscope for identifying the physeal cartilage but not resecting and visualizing the physeal bar simultaneously were excluded from this study.ResultsIn total, nine patients with ten related joints were included in this study. All the patients were followed up for at least two years. The average following time was 28.5 ± 6.7 months. Eight patients with nine related joints had an improvement of angular deformity, averaging 8.3 ± 6.9 degrees, and one had a worsening of the angular deformity. All the patients had a leg length discrepancy improvement, while four patients still had LLD >1 cm. The surgery time was 3.1 ± 0.7 h. There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury.ConclusionsUsing clamps to form a closed osteocavity could make physeal bar resection under all-inside arthroscopic visualization feasible, which is minimally invasive, accurate, and safe.

Chronic wounds are characterized by prolonged healing processes and poor prognoses, which have substantially impacted human health and daily life. Traditional treatment strategies have various limitations and drawbacks. Therefore, fully effective therapeutic approaches remain urgently needed. Stem cell (SC)-based therapies have drawn significant attention for their abilities of immunomodulation and pro-regeneration. It has been demonstrated that stem cells (SCs) can improve angiogenesis, collagen deposition, and hair rejuvenation, thus facilitating wound healing. In addition, attempts were performed to facilitate the cell survival, function, retention, and engraftment of the delivered SCs. In this review, we first introduce the pathological process involved in chronic wound healing. Following that, the mechanism of SCs in promoting chronic wound repair is discussed in detail. Then, we highlight recent SC-based therapies for chronic wound repair developments. Finally, we present our views on the remaining challenges and future trends of SC-based therapies for chronic wound treatment.

Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).

Abstract Purpose To evaluate the outcomes of distal femoral, proximal tibial, and distal tibial physeal bar resection combined with or without the Hemi-Epiphysiodesis procedure and provide a better understanding of the application of physeal bar resection combined with Hemi-Epiphysiodesis procedure in the treatment of physeal bar growth arrest. Methods We retrospectively reviewed the patients who suffered physeal bar and underwent physeal bar resection with or without the Hemi-Epiphysiodesis technique during 2010–2020. All were followed up for at least 2 years or to maturity. A modified mapping method was used to determine the area of a physeal bar by CT data. The aLDFA, aMPTA, aLDTA, MAD, and LLD were measured to assess the deformity of the lower limb. Results In total, 19 patients were included in this study. The average age was 8.9 years (range 4.4 to 13.3 years old). During the follow-up, 4 (21.1%) patients had an angular change 5° averaging 10.0° (range 5.3° to 23.2°), and 3 (15.8%) patients had improvement of the angular deformity averaging 16.8° (range 7.4° to 27.1°). Eleven patients (57.9%) had significant MAD improvement. After surgery, we found that 7 (36.8%) patients had an LLD change of 5 mm averaging 1.0 cm (range 0.7 to 1.3 cm), and 7 (36.8%) patients had increasing of LLD > 5 mm averaging 1.3 cm (range 0.5 to 2.5 cm). There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury. Conclusion Physeal bar resection combined with Hemi-epiphysiodesis is helpful for partial epiphysis growth arrest. Without statistically verifying, we still believe that patients with limited growth ability could benefit more from physeal bar resection combined with Hemi-epiphysiodesis.

In Longyan City, Fujian Province, a hub for premium tobacco in China, our study explored the connection between soil properties and heavy metal levels in tobacco leaves, focusing on chromium (Cr), lead (Pb), and zinc (Zn). We observed that the soil’s average concentrations for Cr, Pb, and Zn were 0.165, 9.53, and 5.17 mg kg ^−1 , respectively. In stark contrast, tobacco leaves presented elevated mean concentrations of these metals, measuring 0.936, 2.19, and 102 mg/kg for Cr, Pb, and Zn, respectively. This disparity was further highlighted by the soil’s exceedance rates for Pb and Zn at 2.93% and 0.472%, and the significantly higher enrichment coefficients in tobacco, 23.1 for Pb and 19.7 for Zn, compared to Cr, suggesting a substantial health risk. Our study identified critical soil parameters, including pH, organic matter, and levels of available potassium and phosphorus, as influential factors determining heavy metal content in tobacco. Utilizing these findings, we formulated predictive regression models for estimating Cr, Pb, and Zn concentrations in tobacco leaves. The regression models for estimating the concentrations of chromium, lead, and zinc in tobacco leaves are as detailed below: Y _Cr = 0.889 + 0.001 * X _K + 0.001 * X _N − 0.005 * X _OM + 0.101 * X _Cr (R ^2 = 0.852), Y _Pb = 2.608–0.069 * X _pH − 0.001 * X _N + 0.008 * X _Zn + 0.01 * X _Pb (R ^2 = 0.738) and Y _Zn = 101.892–0.141 * X _P + 0.32 * X _OM − 0.123 * X _Pb + 0.614 * X _Zn (R ^2 = 0.801), respectively. These offering essential tools for assessing and controlling heavy metal risks in tobacco cultivation within the region.

ABSTRACT Verticillium dahliae is a soilborne fungal pathogen that causes disease on many economically important crops. Based on the resistance or susceptibility of differential cultivars in tomato, isolates of V. dahliae are divided into three races. Avirulence (avr) genes within the genomes of the three races have also been identified. However, the functional role of the avr gene in race 3 isolates of V. dahliae has not been characterized. In this study, bioinformatics analysis showed that VdR3e, a cysteine-rich secreted protein encoded by the gene characterizing race 3 in V. dahliae, was likely obtained by horizontal gene transfer from the fungal genus Bipolaris. We demonstrate that VdR3e causes cell death by triggering multiple defense responses. In addition, VdR3e localized at the periphery of the plant cell and triggered immunity depending on its subcellular localization and the cell membrane receptor BAK1. Furthermore, VdR3e is a virulence factor and shows differential pathogenicity in race 3-resistant and -susceptible hosts. These results suggest that VdR3e is a virulence factor that can also interact with BAK1 as a pathogen-associated molecular pattern (PAMP) to trigger immune responses. IMPORTANCE Based on the gene-for-gene model, research on the function of avirulence genes and resistance genes has had an unparalleled impact on breeding for resistance in most crops against individual pathogens. The soilborne fungal pathogen, Verticillium dahliae, is a major pathogen on many economically important crops. Currently, avr genes of the three races in V. dahliae have been identified, but the function of avr gene representing race 3 has not been described. We investigated the characteristics of VdR3e-mediated immunity and demonstrated that VdR3e acts as a PAMP to activate a variety of plant defense responses and induce plant cell death. We also demonstrated that the role of VdR3e in pathogenicity was host dependent. This is the first study to describe the immune and virulence functions of the avr gene from race 3 in V. dahliae, and we provide support for the identification of genes mediating resistance against race 3.

AbstractContext The reduction in M2 macrophage polarisation plays a major role during diabetic wound healing. Resveratrol (RSV) can promote the polarisation of M2 macrophages and accelerate diabetic wound healing. However, the specific mechanism by which RSV regulates M2 macrophage polarisation to promote diabetic wound healing is unclear.Objective This study evaluated the effectiveness of RSV on diabetic wound healing and analysed the underlying mechanisms.Materials and methods STZ-induced C57/B6 mice were used as a diabetic mice model for a period of 15 days. RSV (10 μmol/L) was injected around the wound to evaluate the effect of RSV on the healing process of diabetic wounds. The human monocyte line THP-1 was used to evaluate the effects of RSV (10 μmol/L) on polarisation of M2 macrophages and the secretion of pro-inflammatory factors.Results In vivo, RSV significantly increased diabetic wound healing (p

In cell-assisted lipotransfer, adipose-derived stem cells play a crucial role in enhancing fat graft retention. In vitro, human adipose-derived stem cells were modified with Bcl-2 gene. In vivo, aspirated fat was mixed with the Bcl-2-modified adipose-derived stem cells and then transplanted subcutaneously into nude mice. The retention of fat graft was evaluated. The surviving Bcl-2-modified adipose-derived stem cells were tracked after transplantation. Capillary density was quantified after transplantation. Transplantation with Bcl-2-modified adipose-derived stem cells enhanced fat graft retention by 49% and 114% at 6 weeks compared with the Fat + vector-modified adipose-derived stem cell group and Fat-only group, respectively. Transplants from the Fat + Bcl-2-modified adipose-derived stem cell group had significantly more intact adipocytes and lower levels of fat necrosis and fibrosis at 6 weeks. The survival of Bcl-2-modified adipose-derived stem cells increased by 33% at 3 weeks and 54% at 6 weeks, respectively, compared with vector-modified adipose-derived stem cells. The capillary density was 24% higher in Fat + Bcl-2-modified adipose-derived stem cell group than in Fat + vector-modified adipose-derived stem cell group or 60% higher than in Fat-only group at 3 weeks.

Study region: Guangdong-Hong Kong-Macao Greater Bay Area urban agglomeration (GBA). Study focus: Existing Water Evaluation and Planning System (WEAP) lacks consideration of regional and industrial water distribution priority. This study proposes an improved WEAP model by integrating regional and industrial water distribution priority determined by water supply safety. The logistic curve model was introduced for water supply safety evaluation. The improved WEAP model was applied to the water resources allocation of GBA in the year of 2019 and 2030, and the effects of water allocation schemes with different regional and industrial water distribution priorities were compared. New hydrological insights of the region: The results indicate that the water supply safety of each city in the GBA varies with region and industry, Guangzhou, Shenzhen and Dongguan have lower degree of domestic and industrial water supply safety. River and reservoir connections are essential to the water supply safety of GBA. The water demands of Shenzhen and Dongguan cannot be satisfied during dry period in 2019, while perfectly satisfied during the dry period in 2030 due to the operation of water transfer projects. The improved WEAP model obtained more reasonable water allocation results, improving the water satisfaction rates of regions with low water supply safety. The research demonstrates the advantage of the improved WEAP model considering regional and industries priority, enhancing the applicability of the WEAP model.

Purpose To investigate the diurnal variation in subfoveal choroidal thickness (SFCT) during the waking period over three consecutive days in different degrees of myopia and emmetropia. Methods A total of 60 adult volunteers were grouped into low, moderate, high myopia, and emmetropia subgroups. SFCT, axial length (AL), anterior chamber depth (ACD), and intraocular pressure (IOP) were measured every 2 h from 8 AM to 8 PM for three successive days. Results The mean values of daily change amplitude were 3.18 mmHg (IOP), 0.05 mm (AL), 0.17 mm (ACD), and 13.51 μm (SFCT). The values of AL and ACD increased simultaneously with spherical equivalent refraction (SER), but SFCT was the opposite. IOP had a diurnal variation, and there was no difference among the four groups. AL of the high myopia group, ACD of the emmetropia group, and SFCT of each myopia group had diurnal variation over three consecutive days. AL had a high mean value at noon every day, and SFCT had a low mean value at noon every day. Conclusion The choroid thickness of subjects with different degrees of myopia had a significant diurnal variation. The change of diurnal variation between emmetropic and myopic subjects may be one of the causes of myopia.

Abstract Background Congenital pseudarthrosis of the tibia (CPT) is a rare disease occurring in children. The aim of this study is to identify the factors affecting bone union and re-fracture after surgery for CPT and to provide reliable evidence for clinics. Methods We collected the detailed information of 255 cases with Crawford IV CPT treated by combined surgery in our hospital from 2013 to 2020. Basic characteristics were recorded. Univariate variance and logistic regression analysis were used to compare the correlations between factors and outcomes. Results 92.5% of patients achieved primary union, 7.5% of patients had non-union and 13.3% of patients had re-fracture. Logistic regression analysis showed that age at index surgery (Coef. = 0.171, 95%CI 0.015–0.327, P = 0.032), and CPT location (Coef. = − 1.337, 95%CI − 2.218–0.456, P = 0.003) had statistical differences, while no factors had significant correlation with re-fracture. Furthermore, ROC curve showed that the optimal age threshold for first surgery was 2.37 years old. Conclusions For patients with Crawford IV CPT treated by combined surgery, the younger the age at index surgery and the closer the CPT location to the distal end, the easier to achieve bone union.

Abstract Hunting the advanced threats hidden in the enterprise networks has always been a complex and difficult task. Due to the variety of attacking means, it is difficult for traditional security systems to detect threats. Most existing methods analyze log records, but the amount of log records generated every day is very large. How to find the information related to the attack events quickly and effectively from massive data streams is an important problem. Considering that the knowledge graph can be used for automatic relation calculation and complex relation analysis, and can get relatively fast feedback, our work proposes to construct the knowledge graph based on kernel audit records, which fully considers the global correlation among entities observed in audit logs. We design the construction and application process of knowledge graph, which can be applied to actual threat hunting activities. Then we explore different ways to use the constructed knowledge graph for hunting actual threats in detail. Finally, we implement a LAN-wide hunting system which is convenient and flexible for security analysts. Evaluations based on the adversarial engagement designed by DARPA prove that our platform can effectively hunt sophisticated threats, quickly restore the attack path or assess the impact of attack.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with a median survival time of 3–5 years. Inaccurate diagnosis, limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need. In recent years, it was reported that DDRs are potential targets in anti-fibrosis treatment. Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases, such as RET, AXL and ALK. Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities, low toxicity, good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy. Therefore, we confirmed that discoidin domain receptors are promising drug targets for IPF, and compound 47 would be a promising candidate for further drug development.

Background: The aim of lymph node dissection for melanoma patients is to prevent metastasis. However, this procedure is accompanied by a long-term and impaired life-quality complication called extremity lymphedema. This condition involves long-term lower limb swelling, which causes discomfort and impaired function, and affects patients both physically and psychologically. Herein, we conducted a retrospective cohort study at a single center to investigate the risk factors associated with lower extremity lymphedema after inguinal lymphadenectomy. Materials and Methods: We identified 136 inguinal lymphadenectomy melanoma patients treated between January 2010 and January 2021. The patients' demographic, clinical, and pathological data and postoperative outcomes were collected by electronic medical record review and patient follow-up. The patients' postoperative outcomes were defined as lower extremity swelling and lower extremity lymphedema. Univariate and multivariate analyses were used to determine the independent predictors of lower extremity lymphedema. Results: The follow-up results from 85 melanoma patients who underwent inguinal lymphadenectomy were analyzed. Multivariate logistic regression analysis showed that number of lymph nodes removed≥10 was the significant risk factor for postoperative lower extremity lymphedema (odds ratio = 6.468, P = .042, 95% confidence interval: 1.069 to 39.147). Moreover, 8 (100%) patients in the lower extremity lymphedema group and 32 (53.3%) patients in the normal group were female, which indicated that female patients might be more susceptible to postoperative lower extremity lymphedema (P = .012). Conclusion: Our study found that number of inguinal lymph nodes removed ≥10 was associated with a significantly higher incidence of lower extremity lymphedema with a 6.5-fold increased risk in melanoma patients. Also, female patients were more likely to develop lower extremity lymphedema after inguinal lymphadenectomy.

Abstract Background Although primary angle-closure glaucoma (PACG) mainly occurs in elderly people, diagnosis of PACG in young patients is not uncommon. So far, there is no article specialized on the ocular anatomical characteristics in these patients.In this study, ocular anatomical characteristics in young PACG patients are analyzed. Methods In this retrospective, comparative study, patients diagnosed with PACG and received ultrasound biomicroscopy (UBM) examination in our department were included. Patients were divided into two groups: a young group composed of patients ≤ 45 years and an old group composed of patients > 45 years. A-scan ultrasonography and ultrasound biomicroscopy (UBM) were used to measure ocular biometric parameters of patients in the two groups including axial length (AL), lens thickness (LT), central anterior chamber depth (ACD), anterior chamber width (ACW), angle opening distance 500 (AOD500), anterior chamber angle 500 (ACA500), iris thickness 1000 μm from the iris root (IT1000), iris thickness 500 μm from the iris root (IT500), trabecular-ciliary process angle (TCPA), trabecular-ciliary process distance (TCPD), scleral– ciliary process angle (SCPA), lens vault (LV), and pupil diameter (PD). Plateau iris (PI) and basal iris insertion were determined from UBM images, and the prevalence of PI and basal iris insertion were compared between the two groups. The incidence of postoperative malignant glaucoma (MG) was also determined in both groups and ocular anatomical predictors for the development of MG were evaluated in young PACG patients. Results One hundred fifteen patients were included into young group and 480 patients were included into old group. The young group had shorter TCPD, shorter AL, narrower TCPA, narrower SCPA thinner Lens compared to the old group. There were no significant differences in ACD, AOD 500, ACA500, LV, IT500, IT1000, PD or ACW between the two groups. The prevalence of PI was 22.6% in old group and 66.1% in young group (P

Longyan City in Fujian Province is one of China’s top-quality tobacco-producing areas and plays an essential role in local economic development. To determine the correlation between heavy metal content in tobacco leaves and soil factors, soil physical and chemical properties and heavy metal contents of lead, cadmium, and copper in tobacco leaves were measured and analyzed by the correlation regression method. The content of lead, cadmium, and copper in soil was determined using hydrochloric acid extraction-AAS and graphite furnace atomic absorption spectrometry. Inductively coupled plasma-mass spectrometry was used to determine heavy metal in tobacco leaf. The findings revealed that the average concentrations of lead, cadmium, and copper in the soil were 12.1, 0.092, and 3.88 mg/kg, respectively. In contrast, the average levels of lead, cadmium, and copper in tobacco leaves were 2.33, 4.89, and 4.35 mg/kg, respectively. The cadmium enrichment coefficient of 54.3 was higher than lead and copper, indicating a greater health risk. Soil pH value was negatively correlated with lead content in tobacco leaf, while potassium and phosphorus nutrient levels were negatively correlated with copper content. In contrast, a positive correlation was established between the presence of organic matter with cadmium content in tobacco leaves. The prediction models of lead, cadmium, and copper in tobacco leaves can be expressed by the regression equation corresponding to each heavy metal as follows: YPb=2.33−0.005∗ XK+0.007∗XN −0.271∗XpH+0.065∗XPb (R2 = 0.787), YCd=1.55+0.012∗XOM−0.014∗XCu+34.6∗XCd (R2 = 0.891), and YCu=4.64−0.029∗XP−0.007∗XK+0.245∗XCu (R2 = 0.724), respectively. The prediction models above provide an effective predictive tool for assessing heavy metal risk in tobacco leaves using soil properties in the study area.

Background. With the rise in diabetes incidence, diabetic foot ulcers have become the most common clinically chronic refractory wounds. Persistent chronic inflammation is a typical feature of diabetic cutaneous wounds, and diabetic wound healing can be improved by alleviating inflammation and oxidative stress. Chick early amniotic fluids (ceAF) consist of native conglutinant substances with balanced amounts of growth factors, cytokines, and chemokines. However, whether ceAF modulates inflammation and oxidative stress and thus promotes diabetic wound healing remains unknown. Materials and Methods. RAW264.7 cells were categorized into four groups: negative control, LPS, LPS + ceAF, and ceAF. 10% of ceAF was selected to treat different groups of mice with a full-thickness skin defect wound. Then, RT-qPCR, western blot, immunofluorescence, and other assays were carried out to explore the effect of ceAF on wound healing and its molecular mechanism. Results. Topical administration of ceAF improved M2 macrophage polarization and inflammatory response in the wound tissues, thereby ameliorating delayed wound healing. Histological improvement could be observed in the grade of inflammation, collagen deposition, and neovascularization in wound edge tissues. ceAF also increased M2 macrophage-specific markers expression and exogenous ceAF suppressed LPS-induced cellular inflammatory response in vitro high glucose environment. Additionally, ceAF could activate TLR4/NF-κB and Nrf2 signal transductions to promote M2 macrophage polarization in vitro. Conclusions. In summary, ceAF downregulates inflammatory response, regulates M2 macrophage transition via TLR4/NF-κB and Nrf2 signaling pathways, and thus improves diabetic wound healing.

Abstract Background We present a unique case of primary breast CD20-positive extranodal NK/T cell lymphoma with stomach involvement in a young Chinese female patient. Case presentation The patient presented with a mass in her right breast that rapidly increased in size over approximately 2 months. Upper gastrointestinal endoscopy showed a giant serpentine ulcer in the stomach. Biopsy was performed, and microscopic inspection revealed that the fibrous tissue was diffusely involved by medium to large abnormal lymphocytes. The cytoplasm was low to moderate. The tumor cells had irregular nuclei and inconspicuous nucleoli. The lymphoid cells were strongly immunoreactive to CD20, CD3, CD4, CD56, TIA-1, EBER, and Ki-67 (90%). Epstein-Barr virus genomes were also found in tumor cells by in situ hybridization. A whole-body positron emission tomography (PET)-CT scan revealed intense FDG uptake in the right breast and greater curvature of the stomach. Monoclonal rearrangements of the T cell receptor (TCR-γ) and immunoglobulin heavy chain (IgH) were identified by genetic analysis. Whole-genome next-generation sequencing was performed, and up to 12 gene mutations, including a frameshift mutation in exon 4 of the BCOR (G97Rfs*87; 44.3%) gene and a base substitution mutation (Q61H 17.6%) in exon 3 of the KRAS gene, were detected. Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the database for annotation, visualization, and integrated discovery, which showed that rare primary breast CD20-positive extranodal NK/T cell lymphoma had a unique genetic background compared with diffuse large B cell lymphoma and extranodal NK/T cell lymphoma without CD20 expression. The patient received four cycles of the modified SMILE regimen. The second whole-body PET-CT scan revealed that the right breast mass was significantly smaller than before; additionally, FDG uptake in the stomach wall disappeared. Conclusions Systemic examination, extensive immunohistochemistry, and molecular profiling are essential for an accurate diagnosis. More similar cases are required to clarify the biological pathways and even the potential molecular mechanisms of rare lymphomas, which may help direct further treatment.

Abstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury‐induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation‐independent manner. Other mechanisms are involved in the pro‐apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS.

PurposeTo identify the iris morphology-related factors for prediction of outcomes of excessively low vault (< 100 μm) after Implantable Collamer Lens V4c (ICL V4c; STAAR Surgical) implantation.MethodsThis retrospective case-control study included 81 eyes from 2,080 patients who underwent ICL implantation. Twenty-seven eyes of 27 patients with excessively low vault (< 100 μm) constituted the case group (excessively low vault group). Patients with vault (250 to 750 μm) were selected as the optimal vault group by matching anterior chamber depth, white-to-white distance and ICL size with cases with excessive low vault (< 100 μm) at a proportion of 1:2. The preoperative biometric parameters and postoperative vault were recorded. Multiple linear regression analysis was performed to assess the relationship between the postoperative vault and various variables. Conditional logistic regression analysis was used to estimate the risk factors for excessively low vault.ResultsThe postoperative vault was associated with preoperative pupil diameter (PD), crystalline lens rise, iris concavity and the ratio of the iris concavity to chord length (P < 0.05). The larger iris concavity increased risk of excessively low postoperative vault (< 100 μm) (OR = 81.10; 95%CI = 2.87 to 2296.58; P = 0.01).ConclusionsEyes with obviously concave iris were associated with a higher rate of excessively low vault (< 100 μm). Evaluation of iris morphology may provide significant information for predicting excessive postoperative vault.