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Abstract Background Soybean seeds are rich in protein and oil. The selection of varieties that produce high-quality seeds has been one of the priorities of soybean breeding programs. However, the influence of improved seed quality on the rhizosphere microbiota and whether the microbiota is involved in determining seed quality are still unclear. Here, we analyzed the structures of the rhizospheric bacterial communities of 100 soybean varieties, including 53 landraces and 47 modern cultivars, and evaluated the interactions between seed quality traits and rhizospheric bacteria. Results We found that rhizospheric bacterial structures differed between landraces and cultivars and that this difference was directly related to their oil content. Seven bacterial families (Sphingomonadaceae, Gemmatimonadaceae, Nocardioidaceae, Xanthobacteraceae, Chitinophagaceae, Oxalobacteraceae, and Streptomycetaceae) were obviously enriched in the rhizospheres of the high-oil cultivars. Among them, Oxalobacteraceae (Massilia) was assembled specifically by the root exudates of high-oil cultivars and was associated with the phenolic acids and flavonoids in plant phenylpropanoid biosynthetic pathways. Furthermore, we showed that Massilia affected auxin signaling or interfered with active oxygen-related metabolism. In addition, Massilia activated glycolysis pathway, thereby promoting seed oil accumulation. Conclusions These results provide a solid theoretical basis for the breeding of revolutionary soybean cultivars with desired seed quality and optimal microbiomes and the development of new cultivation strategies for increasing the oil content of seeds. Video Abstract

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

Summary: Background: Studies from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 can guide screening and prevention strategies for tracheal, bronchus, and lung (TBL) cancer. We aim to provide global, regional, and national estimates of the TBL cancer burden and its attributable risk from 1990 to 2021, including during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Incidence, age-standardised incidence rate (ASIR), deaths, age-standardised mortality rate (ASMR), disability-adjusted life years (DALYs), age-standardised rate of DALYs (ASDR), and the burden due to risk factors associated with TBL cancer were analysed from 1990 to 2021. Trends in ASIR, ASMR, and ASDR of TBL cancer during the COVID-19 pandemic (2019–2021) were also determined. All statistical analyses were performed using Join-point software (version 4.9.1.0). Findings: Between 1990 and 2021, the global incidence, deaths, and DALYs of TBL cancer to varying degrees. However, the ASIR (Average Annual Percent Change [AAPC], −0.3 [−0.4 to −0.2]), ASMR (AAPC, −0.5 [−0.7 to −0.4]), and ASDR (AAPC, −0.9 [−1.0 to −0.7]) all showed a decreasing trend. However, the ASIR, ASMR, and ASDR of TBL cancer in males all showed a decreasing trend from 1990 to 2021. In contrast, the ASIR and ASMR of TBL cancer in females showed an increasing trend, while the ASDR showed a relatively stable trend. During the COVID-19 pandemic, the trends for ASIR, ASMR, and ASDR remained stable across both sexes combined, females, males, five socio-demographic index (SDI) quintiles, and the 21 GBD regions. In 2021, smoking was a major risk factor for TBL cancer DALYs, but the attributable ASDR for smoking decreased from 1990 to 2021 in both sexes combined, as well as individually for males and females. Conversely, the attributable ASDR for secondhand smoke, high fasting plasma glucose and occupational exposure factors increased primarily among females. Furthermore, the attributable ASDR for ambient particulate matter pollution, household air pollution from solid fuels, and low–fruit diets increased primarily in regions with lower SDI quintiles from 1990 to 2021. Interpretation: The burden attributable to TBL cancer has increased in some populations from 1990 to 2021, highlighting the importance of implementing targeted measures to mitigate this trend. No significant change in the burden of TBL cancer was observed during the COVID-19 pandemic; however, post-COVID-19 rates still require further observation. Funding: This study was supported by National Key Research and Development Program of China (2023YFC3503300, 2023YFC3503305), and High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023085, HLCMHPP2023001, HLCMHPP2023097).

IntroductionPostoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%–80% within 2 years after local treatment and approximately 90% within 5 years. “Yang-deficient toxic node” is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of “nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying” can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence.MethodsThe study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1–3 years, cumulative annual survival after 1–3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate.DiscussionThere is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery.Clinical trial registrationClinicalTrials.gov, identifier NCT05229809.

Abstract Background The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. Methods The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. Results PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. Conclusions Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

Existing self-supervised models for monocular depth estimation suffer from issues such as discontinuity, blurred edges, and unclear contours, particularly for small objects. We propose a self-supervised monocular depth estimation network with multi-scale selective Transformer feature fusion. To preserve more detailed features, this paper constructs a multi-scale encoder to extract features and leverages the self-attention mechanism of Transformer to capture global contextual information, enabling better depth prediction for small objects. Additionally, the multi-scale selective fusion module (MSSF) is also proposed, which can make full use of multi-scale feature information in the decoding part and perform selective fusion step by step, which can effectively eliminate noise and retain local detail features to obtain a clear depth map with clear edges. Experimental evaluations on the KITTI dataset demonstrate that the proposed algorithm achieves an absolute relative error (Abs Rel) of 0.098 and an accuracy rate (δ) of 0.983. The results indicate that the proposed algorithm not only estimates depth values with high accuracy but also predicts the continuous depth map with clear edges.

Backgrounds: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. Methods: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger’s test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. Results: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4 + ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4 + /CD8 + ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8 + T cell ratio (MD = −5.25, 95% CI: −5.94 to −4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. Conclusion: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Abstract Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC.

Abstract Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.

The major limitations of photoelectrochemical (PEC) water splitting lies in the currently unsatisfying efficiency and stability of the semiconductor materials-based water splitting systems. By addressing these limitations, the immobilization of the molecular catalysts on semiconductor photoanodes to establish a hybrid inorganic-organic PEC system has attracted an increasing research attention. It is crucial to choose a suitable molecular catalyst and effectively couple it into a hybrid photoelectrode system. In this review, focusing on the water oxidation process, molecular catalysts integrated photoelectrochemical water oxidation systems are highlighted from the perspective of the roles of molecular catalysts and the integration strategies in the hybrid system. The most recent advances are summarized with various case studies presented, based on which perspectives are proposed to provide guidance toward the rational design of an integrated system for future development.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Introduction: Compound Kushen Injection (CKI) is a traditional Chinese medicine extracted from Sophora flavescens Aiton and Heterosmilax japonica Kunth. Widely utilized in China for the comprehensive treatment of colorectal cancer (CRC), this study aims to systematically assess the efficacy and safety of CKI when combined with chemotherapy for the treatment of advanced CRC, based on available data. Methods: Randomized controlled trials investigating the efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC will be comprehensively searched from databases, including PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang, Chinese Biomedicine Database Searches, Chinese Clinical Trial Registry, and ClinicalTrials.gov until November 2022. Two independent reviewers will screen the studies, assess the risk of bias, and extract data in duplicate. The ROB2 tool will be employed to assess the quality of included studies. Stata 16 will be used for data analysis, and publication bias will be assessed using funnel plots and Egger's test. The quality of evidence will be evaluated according to GRADE, and trial sequence analysis (TSA) will be utilized to calculate the final total sample size required for the meta-analysis. The results of this systematic review will be published in a peer-reviewed journal. The proposed review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022380106). Discussion: This systematic review will integrate current evidence on CKI in advanced CRC and analyze the clinical efficacy and safety of CKI combined with different chemotherapy regimens, providing valuable guidance on the use of CKI in CRC patients.

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.

Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells in the tumor microenvironment (TME) that play critical roles in promoting tumor growth and metastasis. Tumor-associated platelets (TAPs) help cancer cells evade the immune system and promote metastasis. In this paper, we describe the interaction between MDSCs and TAPs, including their generation, secretion, activation, and recruitment, as well as the effects of MDSCs and platelets on the generation and changes in the immune, metabolic, and angiogenic breast cancer (BC) microenvironments. In addition, we summarize preclinical and clinical studies, traditional Chinese medicine (TCM) therapeutic approaches, and new technologies related to targeting and preventing MDSCs from interacting with TAPs to modulate the BC TME, discuss the potential mechanisms, and provide perspectives for future development. The therapeutic strategies discussed in this review may have implications in promoting the normalization of the BC TME, reducing primary tumor growth and distant lung metastasis, and improving the efficiency of anti-tumor therapy, thereby improving the overall survival (OS) and progression-free survival (PFS) of patients. However, despite the significant advances in understanding these mechanisms and therapeutic strategies, the complexity and heterogeneity of MDSCs and side effects of antiplatelet agents remain challenging. This requires further investigation in future prospective cohort studies.

Tumor-draining lymph nodes (TDLNs) are potential immunotherapy targets that could expand the population of patients with colorectal cancer (CRC) who may benefit from immunotherapy. Currently, pathological detection of tumor cell infiltration limits the acquisition of immune information related to the resected lymph nodes. Understanding the immune function and metastatic risk of specific stages of lymph nodes can facilitate better discussions on the removal or preservation of lymph nodes, as well as the timing of immunotherapy. This review summarized the contribution of TDLNs to CRC responses to immune checkpoint blockade therapy, local immunotherapy, adoptive cell therapy, and cancer vaccines, and discussed the significance of these findings for the development of diagnostics based on TDLNs and the potential implications for guiding immunotherapy after a definitive diagnosis. Molecular pathology and immune spectrum diagnosis of TDLNs will promote significant advances in the selection of immunotherapy options and predicting treatment efficacy.

BackgroundThe question of whether flexible sigmoidoscopy (FS) for colorectal cancer (CRC) affects incidence or mortality remains unclear. In this study, we conducted a meta-analysis and systematic review to explore this issue.MethodsA systematic search of PubMed, EMBASE, and ClinicalTrials.gov was performed for cohort studies (CS), case–control studies, and randomized controlled trials (RCTs) of people who underwent FS and reported mortality or incidence of CRC until 11 December 2022. Relative risk (RR) was applied as an estimate of the effect of interest. To combine the RRs and 95% confidence intervals, a random-effects model was used. The quality of the included studies and evidence was assessed by the Newcastle-Ottawa quality assessment scale, the Jadad scale, and the “Grading of Recommendations Assessment, Development and Evaluation System.”ResultsThere were a total of six RCTs and one CS, comprising 702,275 individuals. FS was found to be associated with a 26% RR reduction in CRC incidence (RR, 0.74; 95% CI, 0.66–0.84) and a 30% RR reduction in CRC mortality (RR, 0.70; 95% CI, 0.58–0.85). In the incidence subgroup analysis, FS significantly reduced the incidence of CRC compared with non-screening, usual care, and fecal immunochemical testing. Significance was also shown in men, women, distal site, stages III–IV, ages 55–59, and age over 60. In terms of the mortality subgroup analysis, the results were roughly the same as those of incidence.ConclusionAccording to this study, FS might reduce the incidence and mortality of CRC. To confirm this finding, further prospective clinical studies should be conducted based on a larger-scale population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023388925.

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

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.

The EAST ICRF system operating space has been extended in power and phase control with a low-level RF system for the new double-strap antenna. Then the multi-step power and periodic phase scanning experiment were conducted in L-mode plasma, respectively. In the power scanning experiment, the stored energy, radiation power, plasma impedance and the antenna's temperature all have positive responses during the short ramp-ups of PL,ICRF. The core ion temperature increased from 1 keV to 1.5 keV and the core heating area expanded from |Z|≤5cm to |Z|≤10cm during the injection of ICRF waves. In the phasing scanning experiment, in addition to the same conclusions as the previous relatively phasing scanning experiment, the superposition effect of the fluctuation of stored energy, radiation power and neutron yield caused by phasing change with dual antenna, resulting in the amplitude and phase shift, was also observed. The active control of RF output facilitates the precise control of plasma profiles and greatly benefits future experimental exploration.

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.

Background: Congenital pseudarthrosis of the tibia (CPT) is an uncommon congenital deformity and a special subtype of bone nonunion. The lower ability of osteogenic differentiation in CPT-derived mesenchymal stem cells (MSCs) could result in progression of CPT, and miR-30a could inhibit osteogenic differentiation. However, the role of miR-30a in CPT-derived MSCs remains unclear. Methods: The osteogenic differentiation of CPT-derived MSCs treated with the miR-30a inhibitor was tested by Alizarin Red S staining and alkaline phosphatase (ALP) activity. The expression levels of protein and mRNA were assessed by Western blot or quantitative reverse transcription-polymerase chain reaction (RT-qPCR), respectively. The interplay between miR-30a and HOXD8 was investigated by a dual-luciferase reporter assay. Chromatin immunoprecipitation (ChIP) was conducted to assess the binding relationship between HOXD8 and RUNX2 promoter. Results: CPT-derived MSCs showed a lower ability of osteogenic differentiation than normal MSCs. miR-30a increased in CPT-derived MSCs, and miR-30a downregulation promoted the osteogenic differentiation of CPT-derived MSCs. Meanwhile, HOXD8 is a direct target for miR-30a, and HOXD8 could transcriptionally activate RUNX2. In addition, miR-30a could inhibit the osteogenic differentiation of CPT-derived MSCs by negatively regulating HOXD8. Conclusion: miR-30a inhibits the osteogenic differentiation of CPT-derived MSCs by targeting HOXD8. Thus, this study might supply a novel strategy against CPT.

Abstract Background Pancreatic cancer (PC) is a highly malignant tumor which threatens human’s health. Long non-coding RNAs (lncRNAs) are implicated in many cancers, including PC, but their mechanisms in PC have not yet been entirely clarified. We focused on revealing the potential function of lncRNA SOX21-AS1 in PC. Methods Functional assays assessed SOX21-AS1 function on PC progression. Bioinformatics analysis, along with mechanism assays were taken to unmask the regulatory mechanism SOX21-AS1 may exert in PC cells. Results SOX21-AS1 possessed a high expression level in PC cells. SOX21-AS1 absence suppressed PC cell proliferation, migration, stemness and epithelial-mesenchymal transition (EMT) while elevated cell apoptosis. SOX21-AS1 positively regulated its nearby gene SRY-box transcription factor 21 (SOX21) at post-transcriptional level. Through mechanism assays, we uncovered that SOX21-AS1 sponged SOX21-AS1 to elevate SOX21 mRNA and recruited ubiquitin-specific peptidase 10 (USP10) to deubiquitinate and stabilize SOX21 protein. Moreover, signal transducer and activator of transcription 6 (STAT6) could transcriptionally activate SOX21-AS1 and SOX21 expression. Conclusions SOX21-AS1 aggravated the malignant development of PC, which might provide the utility value for PC treatment.

Abstract Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.

Background: Depression is one of the common complications in patients with postoperative breast cancer (BC). Conventional therapies for postoperative depression of BC always have modest treatment outcomes and undesirable side effects. Clinical practice and many studies have shown that traditional Chinese medicine (TCM) has a good effect on postoperative depression of BC. This meta-analysis aimed to assess the clinical effect of TCM as an add-on treatment for postoperative depression of BC.Methods: A systematic and thorough search was conducted on eight online electronic databases up to 20 July 2022. The control group received conventional therapies, and intervention groups received what control groups received plus TCM treatment. Review Manager 5.4.1 was used for statistical analysis.Results: Nine RCTs involved 789 participants who met the inclusion standards. The results showed the intervention group was better at decreasing the score of the Hamilton rating scale for depression (HAMD) (mean difference, MD = −4.21, 95% CI −5.54 to −2.88) and the self-rating depression scale (SDS) (MD = −12.03, 95% CI −15.94 to −8.13), improving clinical efficacy (RR = 1.25, 95% CI 1.14–1.37), increasing the levels of 5-hydroxytryptamine (5-HT) (MD = 0.27, 95% CI 0.20–0.34), dopamine (DA) (MD = 26.28, 95% CI 24.18–28.77), and norepinephrine (NE) (MD = 11.05, 95% CI 8.07–14.04), and influencing the immune index, including the levels of CD3+ (MD = 15.18, 95% CI 13.61–16.75), CD4+ (MD = 8.37, 95% CI 6.00–10.74), and CD4+/CD8+ (MD = 0.33, 95% CI 0.27–0.39). The level of CD8+ (MD = −4.04, 95% CI −11.98 to 3.99) had no obvious difference between the two groups.Conclusion: The meta‐analysis stated that a therapeutic regimen involving TCM could better improve the depression status in postoperative BC.

Importance: It is necessary to determine whether safety and efficacy of autologous skin tissue cells grafting for facial sunken or flat scars. Objective: To identify autologous skin tissue cells grafting can reduce facial sunken or flat scars. Design, setting, and participants: In this retrospective cross-sectional study, a total of 128 patients with scar (exclude pathological scar patients), who were receiving autologous skin tissue cells grafting therapy from January 1, 2016, to December 31, 2019. Interventions: Autologous skin tissue cells grafting. Main outcomes and measures: Changes in scar severity, color changes in the scar area, infection rate and patient satisfaction. Results: A total of 128 patients with scar (89 females [69.5%]; mean [SD] age, 30.6 [13.12] years) received autologous skin tissue cells grafting therapy. SCAR (Scar Cosmesis Assessment and Rating), with scores ranging from 0 (best possible scar) to 15 (worst possible scar). After treatment 12 months, the mean [SD] of SCAR score went down from 9.85 [1.33] to 2.67 [1.21]. No infection was observed during treatment or recovery, and the main drawback after autologous skin tissue cells grafting is that the color recovery time is longer. The patient satisfaction 6 months after treatment was 85.2%, furthermore 12 months after treatment patient satisfaction was 94.7%. Conclusions and relevance: In this study, autologous skin tissue cells grafting was safe and effective to treat facial scars. Therefore, autologous skin tissue cells grafting may be recommended as a reliable treatment for facial scar.

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.

In the realm of data protection strategies, differential privacy ensures that unauthorized entities cannot reconstruct original data from system outputs. This study explores discrete event systems, specifically through probabilistic automata. Central is the protection of state data, particularly the initial state privacy of multiple starting states. We introduce an evaluation criterion to safeguard initial states. Using advanced algorithms, the proposed method counters the probabilistic identification of any state within this collection by adversaries from observed data points. The efficacy is confirmed when the probability distributions of data observations tied to these states converge. If a system’s architecture does not meet state differential privacy demands, we propose an enhanced supervisory control mechanism. This control upholds state differential privacy across all initial states, maintaining operational flexibility within the probabilistic automaton framework. Concluding, a numerical analysis validates the approach’s strength in probabilistic automata and discrete event systems.

Abstract Background Reconstruction of large tibial defects is often a major challenge in limb salvage. This study aimed to evaluate initial follow-up results of ipsilateral fibula transfer for the treatment of large tibial defects in children. Methods A retrospective study was performed between September 2014 and April 2021. Ten children were identified as having large tibial defects. The children underwent ipsilateral fibula transfer. We then evaluated initial healing, tibial length discrepancy, ankle varus/valgus, fibular position, refracture, infection, and function. Results Five boys and five girls, with an average age of 7.2 years, were evaluated. The transferred fibula was united in the patients. The mean follow-up period after fibular transposition was 43 months. The patients achieved primary bone union; the mean time to union was 8.4 months (range, 4–18 months). Complications included refracture (30%), infection (40%), tibia malunion (30%), ankle varus (30%), sensory loss of toes (10%), and ankle valgus (10%). No other major complications were observed. All 10 patients were able to perform activities of daily living and return to their normal activities. Conclusion Ipsilateral fibula transfer is a salvage surgery for the treatment of large tibial defects in children with congenital pseudoarthrosis of the tibia, traumatic nonunion of the tibia, and/or tibial defect after chronic osteomyelitis. However, long-term results still need to be followed up.

Changes in cellular metabolism involving fuel sources are well-known mechanisms of cancer cell differentiation in the context of carcinogenesis. Metabolic reprogramming is regulated by oncogenic signaling and transcriptional networks and has been identified as an essential component of malignant transformation. Hypoxic and acidified tumor microenvironment contributes mainly to the production of glycolytic products known as lactate. Mounting evidence suggests that lactate in the tumor microenvironment of colorectal cancer(CRC) contributes to cancer therapeutic resistance and metastasis. The contents related to the regulatory effects of lactate on metabolism, immune response, and intercellular communication in the tumor microenvironment of CRC are also constantly updated. Here we summarize the latest studies about the pleiotropic effects of lactate in CRC and the clinical value of targeting lactate metabolism as treatment. Different effects of lactate on various immune cell types, microenvironment characteristics, and pathophysiological processes have also emerged. Potential specific therapeutic targeting of CRC lactate metabolism is also discussed. With increased knowledge, effective druggable targets might be identified, with the aim of improving treatment outcomes by reducing chemoresistance.

The use of electric vehicles is for reducing carbon emissions, thereby reducing environmental pollution caused by transportation. However, the large-scale production and application of electric vehicle batteries have brought another notable issue, i.e., the production and application of these batteries also cause environmental pollution. Particularly, the precious metal materials used in the batteries are harmful to human health and the surrounding ecological system. Nowadays, many types of batteries are available. It is essential to understand which of them is most suitable for electric vehicles from the perspective of environmental protection. To answer this question, the life cycle environmental impact assessment of LiFePO 4 battery and Li(NiCoMn)O2 battery, which are being popularly used in pure electric passenger vehicles, are conducted in this paper. The research has shown that the two types of batteries show different environmental impact features in different phases. For example, LiFePO 4 batteries are more environmentally friendly in the phase of production, while Li(NiCoMn)O2 batteries are more eco-friendly in the application and transportation phases. Despite this, LiFePO 4 batteries are generally more environmentally friendly than Li(NiCoMn)O2 batteries from the perspective of the entire life cycle. In addition, the research results also suggest that due to the heavier mass, LiFePO 4 batteries can probably gain more benefit when used for energy storage.

This paper addresses the fault diagnosis problem of PLC-based systems that can be modeled as Petri nets under a certain level of abstraction. The existing Petri-net-based fault diagnosis approaches often associate transitions and/or places with sensors and require that any change in sensor readings needs to be treated by a PLC, leading to a situation that the PLC would be too busy processing the changes in sensor readings to perform other tasks. This paper assumes that a PLC does not monitor the changes of readings of sensors all the time, but periodically reads the values of sensors when needed. The system output is defined as a marking sequence interleaved with possible observed transitions. A fault diagnosis algorithm is developed by defining and solving integer linear programing (ILP) problems whose size is regardless of the length of the system output. The proposed approach enjoys high computational efficiency compared with other ILP-based approaches and is more suitable for fault diagnosis of PLC-based systems with low computing power.

Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, anti-fibrotic, central nervous system modulating, cardioprotective, and immune-enhancing effects. Numerous studies have also shown that throuth multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Futhermore, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors.

Abstract Background The current surgical treatment of choice is the combination surgical technique, involving tibial intramedullary fixation to maintain the mechanical axis and mechanical stability of tibial pseudarthrosis. In traditional combined surgery, the Williams rod is often used. Long-term intramedullary fixation of the foot and ankle will affect the ankle joint function of children. The intramedullary rod is relatively shorter due to the growth of the distal tibia. In addition, there are some complications such as epiphyseal bone bridge and high-arched foot. The use of a telescopic intramedullary rod may avoid these complications. Purposes To investigate the initial effect of the “telescopic rod” in a combined surgical technique for the treatment of congenital pseudarthrosis of the tibia in children. Methods A retrospective study including 15 patients with Crawford type IV CPT who were treated using a combined surgical technique and the telescopic rod from January 2017 to May 2018. The average age at the time of surgery was 43.3 months (16–126 months). Of the 15 patients, 7 had proximal tibia dysplasia and 12 exhibited neurofibromatosis type 1. The combined surgical technique using the telescopic rod included the excision of pseudarthrosis, intramedullary rod insertion, installation of Ilizarov’s fixator, tibia-fibular cross union, and wrapping autogenic iliac bone graft. The incidence of refracture, ankle valgus, tibial valgus, and limb length discrepancy (LLD) in patients were investigated. Results All patients achieved primary union with an average follow-up time of 37.3 months (26–42 months). The mean primary union time was 4.5 months (4.0–5.6 months). Nine cases showed LLD (60%), with an average limb length of 1.1 cm (0.5–2.0 cm). Ankle valgus, proximal tibial valgus, telescopic rod displacement, and epiphyseal plate tethering occurred in 1 case (6.6%) (18°), 3 cases (20%) (10°, 5°, and 6°, respectively), 6 cases (40%), and 2 cases (13%), respectively. There were no refractures during the follow-up periods. Conclusion Although there are complications such as intramedullary rod displacement while using the telescopic rod in a combined surgery, the primary healing rate of congenital pseudarthrosis of the tibia in children is high.

BackgroundCongenital pseudarthrosis of the tibia (CPT) is a refractory and rare disease. Because of its extremely low incidence, little is known about its clinical features. In this retrospective study, we aim to analyze the clinical characteristics of patients with CPT.Materials and methodsThis is a retrospective study of children with CPT identified by the radiological review. Investigations of CPT included general conditions, the characteristics of CPT, treatment methods, and surgical complications.ResultsWe collected 514 CPT cases from March 1999 to March 2020 in our hospital, such as 317 (61.67%) boys, 197 (38.33%) girls; 330 (62.86%) in Crawford IV; 510 (97.14%) in mid and distal 1/3 tibia; 481 (93.58%) in less than 3 years at onset age; 297 (57.78%) in less than 3 years at the first outpatient visit. The most common post-operative complication was ankle valgus (101, 39.60%), followed by limb length discrepancy (91, 35.69%), refracture (38, 14.90%), osteomyelitis (15, 5.88%), and removal of internal fixation (10, 3.93%).ConclusionsCPT with a higher incidence of Crawford IV frequently occurs in boys and the middle or distal part of the tibia; most patients have the onset age and first outpatient visit before 3 years; the major surgical complications are ankle valgus and limb length discrepancy.

Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy.Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs.Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as “Some concerns” of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC.Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research.Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262595], identifier [CRD42022262595].

Background: Distraction osteogenesis (DO) is an approach for bone lengthening and reconstruction. The pixel value ratio (PVR), an indicator calculated from X-ray images, is reported to assess the final timing for the external fixator removal. However, the early PVR and its potential influencing factors and the relationship between the early PVR and clinical outcomes are rarely discussed. Therefore, this study was employed to address these issues.Methods: A total of 125 patients with bone lengthening were investigated retrospectively. The early PVR of regenerated bone was monitored in the first 3 months after osteotomy. The potential effect of sex, chronological age, BMI, lengthening site, and involvement of internal fixation during the consolidation period was analyzed. Moreover, the associations of the healing index (HI) and lengthening index (LI) with early PVR were also investigated.Results: The early PVRs were 0.78 ± 0.10, 0.87 ± 0.06, and 0.93 ± 0.06 in the first 3 months after osteotomy, respectively. Moreover, the PVR in juvenile was significantly higher than that in adults in the first 3 months after osteotomy (0.80 ± 0.09 vs. 0.74 ± 0.10; p = 0.008), (0.89 ± 0.06 vs. 0.83 ± 0.06; p = 0.018), and (0.94 ± 0.05 vs. 0.87 ± 0.05; p = 0.003). In addition, the PVR in males was significantly higher than that in females in the first month after osteotomy (0.80 ± 0.09 vs. 0.76 ± 0.10; p = 0.015), and the PVR in femur site was significantly higher than that in the tibia site in the second and third months after osteotomy (0.88 ± 0.07 vs. 0.87 ± 0.06; p = 0.015) and (0.93 ± 0.06 vs. 0.92 ± 0.06, p = 0.037). However, the BMI and involvement of the internal fixator during the consolidation period seem to not influence the early PVR of regenerated callus during DO. Interestingly, the early PVR seems to be moderately inversely associated with HI (mean = 44.98 ± 49.44, r = -0.211, and p = 0.029) and LI (mean = 0.78 ± 0.77, r = -0.210, and p = 0.029), respectively.Conclusion: The early PVR is gradually increasing in the first 3 months after osteotomy, which may be significantly influenced by chronological age, sex, and the lengthening site. Moreover, the early PVR of callus may reflect the potential clinical outcome for DO. Our results may be beneficial to the clinical management of the subjects with bone lengthening.

Cancer continues to pose a severe threat to global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in managing cancer, encounter considerable challenges, including drug resistance, poor drug solubility, and difficulties targeting tumors, specifically limiting their overall efficacy. Nanomedicine’s application in cancer therapy signals a new epoch, distinguished by the improvement of the specificity, efficacy, and tolerability of cancer treatments. This review explores the mechanisms and advantages of nanoparticle-mediated drug delivery, highlighting passive and active targeting strategies. Furthermore, it explores the transformative potential of nanomedicine in tumor therapeutics, delving into its applications across various treatment modalities, including surgery, chemotherapy, immunotherapy, radiotherapy, photodynamic and photothermal therapy, gene therapy, as well as tumor diagnosis and imaging. Meanwhile, the outlook of nanomedicine in tumor therapeutics is discussed, emphasizing the need for addressing toxicity concerns, improving drug delivery strategies, enhancing carrier stability and controlled release, simplifying nano-design, and exploring novel manufacturing technologies. Overall, integrating nanomedicine in cancer treatment holds immense potential for revolutionizing cancer therapeutics and improving patient outcomes.

Abstract Background Non-small-cell lung cancer (NSCLC) is usually diagnosed at an advanced stage, and chemotherapy is the main treatment for this disease. Kanglaite injections (KLTi) have been widely used for the treatment of cancer in China. KLTi combined with chemotherapy could improve the short-term efficacy, quality of life, and performance status for NSCLC compared with chemotherapy alone. This trial aims to assess the long-term efficacy and safety of KLTi in combination with chemotherapy for the treatment of advanced NSCLC. Methods This will be an investigator-initiated multicenter open-label randomized controlled trial. We will randomly assign 334 eligible participants with stage IIIA-IV NSCLC to the treatment or control groups in a 1:1 ratio. Patients in both groups will be administered 4–6 cycles of first-line platinum-based double chemotherapy regimens. Patients with complete response, partial response, or stable disease after 4–6 cycles will receive non-platinum single-agent chemotherapy. Patients in the treatment group are to receive intravenous KLTi 200 ml per day continuously for 14 days, commencing on the first day of chemotherapy. The treatment will be discontinued at the time of disease progression or until unacceptable toxicity is noted. The follow-up will be conducted every 2 months until death, loss of follow-up, or 12 months from randomized enrollment. The primary outcome will be progression-free survival (PFS). The secondary outcomes will be the objective response rate, 1-year survival rate, quality of life, living ability, and blood lipids. The safety outcome will be the rate of adverse events. Discussion This study will be the first randomized controlled trial in which PFS is used as the primary outcome to test whether KLTi combined with first-line chemotherapy has superior efficacy and reduced toxicity compared to chemotherapy alone in advanced NSCLC. This will also be the first clinical study to observe the effects of KLTi on blood lipids. Trial registration ClinicalTrials.gov NCT03986528 . Prospectively registered on 30 May 2019.

Abstract As a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

Abstract Food is the paramount necessity of the people, while food safety is the priority. Facing the increasingly serious food safety problems in China, how to improve food safety has become the responsibility of the whole society, and also the obligation of social development. Based on the 8000 residents’ survey data, the ordinal logistic model was used to analyze the residents’ satisfaction with food safety. The results show that residents are generally worried about food safety, and there is a strong demand for safe food. Gender, age, educational background, supervision, publicity, and complaint handling significantly affect residents’ food safety satisfaction. In terms of income heterogeneity, low-income residents have the highest degree of satisfaction with food safety. With the improvement of income level, their degree of satisfaction is decreasing. The high-income class residents have a strong consciousness of rights safeguarding after purchasing unsafe food. For low-income residents, their awareness of rights protection is declining due to insufficient income. In the way of rights protection, most respondents choose to return or refund money after negotiation with the seller. The lack of punishment for unscrupulous sellers is one of the main reasons for the frequent occurrence of food safety problems in China.

Background: Health authorities recommend influenza vaccination to diabetic patients. Nevertheless, the vaccination coverage of adults was low in China. This study aimed to estimate influenza vaccination intentions and actual uptake among diabetic patients in China and identify the motivators and barriers associated with vaccination. Methods: During Nov 2016–Jan 2017, 1960 diabetic patients were invited to participate in the investigation about influenza vaccination based on health belief model (HBM). To link vaccination intention to behavior, a follow-up survey was conducted to collect vaccination records of the 2016–2017 season. Predictors of the motivation to obtain influenza vaccination were assessed using logistic regressions. Results: 1914 diabetic patients completed the survey. 46.13% participants reported intentions to be vaccinated against influenza and 7.84% actually received vaccination. In the multivariate models, while all the domains of HBM constructs were associated with intentions, age, increasing numbers of comorbidity, urban residents, perceived susceptibility, perceived benefits, free vaccination, and vaccination history displayed positive associations with vaccine uptake while increasing income and perceptions of barriers were negative predictors of vaccine uptake. Besides, interactions between perceived susceptibility and healthcare workers’ (HCW’s) recommendation, perceived severity and benefits, perceived severity and health-seeking behaviors, perceived benefits, and influence of family/friends had a significant positive effect modification on the vaccine uptake. Conclusion: To improve diabetic patients’ influenza vaccination and close the intention-behavior gap, multipronged strategies are required not only to increase vaccination intention by promoting HCW’s recommendation to improve perceptions about influenza vaccination but also facilitate a follow through on initial intentions by implementing free influenza vaccination program funded by the government.

Background:Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT.MethodsA total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements.Results74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (−0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification.ConclusionsWe found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.

Abstract Background Re-fracture is the most serious complication in congenital pseudarthrosis of the tibia (CPT). There are reports that children with small cross-sectional areas in the sections of the pseudarthrosis are more prone to re-fracture. Presently, preventing complications is a challenge. Increasing the cross-sectional area in healed segments may reduce the incidence of re-fracture. Purpose To elucidate the indications, surgical technique, and outcomes of combined surgery and 3-in-1 osteosynthesis in CPT with intact fibula. Methods We retrospectively assessed 17 patients with Crawford Type IV CPT with intact fibula (Type A) who were treated with combined surgical technique and 3-in-1 osteosynthesis between March 2014 and August 2015. The average age of the patients at the time of surgery was 3 years. Incidence of re-fracture, ankle valgus, proximal tibial valgus, and limb length discrepancy (LLD) were investigated over an average follow-up time of 47 months. Results Primary union was achieved in all patients. The average time for primary union was 4.9 months. Fifteen (88%) cases showed LLD with an average limb length of 1.6 cm; 6 (35%) cases exhibited tibial valgus with an average tibial valgus deformity of 7.8°; 2 cases had ankle valgus, wherein the ankle valgus deformity was 12° in one and 17° in another; and the cross-sectional area of the bone graft was enlarged to 1.74 times that of the tibia shaft. No case had re-fracture during the follow-up period. Movement of the ankle joint was restored in 16 patients with an average dorsiflexion of 22° and an average plantar flexion of 41°; the function of the ankle joint was normal. One patient had plantar flexion of 20° but did not have dorsiflexion. Conclusion Combined surgical technique with 3-in-1 osteosynthesis, which is primarily considered for bone union with a large cross-sectional area, results in a high primary union rate. This can provide satisfactory results in short-term follow-up when treating CPT with intact fibula (Type A).

In this article, we propose an online fault diagnosis approach for labeled Petri nets. When observing an event, the reachability graph of the unobservable subnet (i.e., the net consisting of all places, unobservable transitions, and the attached arcs between them) is first constructed and then a topological sort (i.e., an ordered list of markings) of the reachability graph is obtained. According to the topological sort, each marking in the reachability graph is associated with a vector that contains diagnosis information to form a new graph, called a diagnosis graph. Based on the diagnosis graph constructed for each observed event, an online algorithm is developed to perform diagnosis. When the considered Petri net systems have a small amount of unobservable transitions, the proposed approach enjoys a high computational efficiency compared with the existing ones using integer linear programming.

This paper addresses the fault diagnosis problem in discrete event systems using backward conflict-free Petri nets, where two different transitions have no common output places. The notion of generalized markings is employed, where the number of tokens in a place can be negative. Based on the special structures of backward conflict-free Petri nets and the generalized marking corresponding to an observed transition sequence, an integer linear programming (ILP) problem is constructed where the numbers of unknown integer variables and constraints are independent of the length of the observed transition sequence. A diagnosis algorithm is proposed by associating two different objective functions with the ILP problem and solving it. The computational efficiency of the proposed algorithm depends on the net structure only, regardless of the length of an observed transition sequence.

Background: Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM.Methods: We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus.Results: We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation.Conclusions/interpretation: Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.

Due to the strong heterogeneity of bladder cancer (BC), there is often substantial variation in the prognosis and efficiency of immunotherapy among BC patients. For the precision treatment and assessment of prognosis, the subtyping of BC plays a critical role. Despite various subtyping methods proposed previously, most of them are based on a limited number of molecules, and none of them is developed on the basis of cell states. In this study, we construct a single-cell atlas by integrating single cell RNA-seq, RNA microarray, and bulk RNA-seq data to identify the absolute proportion of 22 different cell states in BC, including immune and nonimmune cell states derived from tumor tissues. To explore the heterogeneity of BC, BC was identified into four different subtypes in multiple cohorts using an improved consensus clustering algorithm based on cell states. Among the four subtypes, C1 had median prognosis and best overall response rate (ORR), which characterized an immunosuppressive tumor microenvironment. C2 was enriched in epithelial-mesenchymal transition/invasion, angiogenesis, immunosuppression, and immune exhaustion. Surely, C2 performed the worst in prognosis and ORR. C3 with worse ORR than C2 was enriched in angiogenesis and almost nonimmune exhaustion. Displaying an immune effective environment, C4 performed the best in prognosis and ORR. We found that patients with just an immunosuppressive environment are suitable for immunotherapy, but patients with an immunosuppressive environment accompanied by immune exhaustion or angiogenesis may resist immunotherapy. Furthermore, we conducted exploration into the heterogeneity of the transcriptome, mutational profiles, and somatic copy-number alterations in four subtypes, which could explain the significant differences related to cell states in prognosis and ORR. We also found that PD-1 in immune and tumor cells could both influence ORR in BC. The level of TGFβ in a cell state can be opposite to the overall level in the tissues, and the level in a specific cell state could predict ORR more accurately. Thus, our work furthers the understanding of heterogeneity and immunotherapy resistance in BC, which is expected to assist clinical practice and serve as a supplement to the current subtyping method from a novel perspective of cell states.