The application potential of iMSCs and iMSC-EVs in diseases.

The immune system, functioning as the body's "defense army", plays a role in surveillance, defense. Any disruptions in immune system can lead to the development of immune-related diseases. Extensive researches have demonstrated the crucial immunoregulatory role of mesenchymal stem cells (MSCs) in these diseases. Of particular interest is the ability to induce somatic cells under specific conditions, generating a new cell type with stem cell characteristics known as induced pluripotent stem cell (iPSC). The differentiation of iPSCs into MSCs, specifically induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), hold promise as a potential solution to the challenges of MSCs, potentially serving as an alternative to traditional drug therapies. Moreover, the products of iMSCs, termed induced pluripotent stem cell-derived mesenchymal stem cell-derived extracellular vesicles (iMSC-EVs), may exhibit functions similar to iMSCs. With the biological advantages of EVs, they have become the focus of "cell-free therapy". Here, we provided a comprehensive summary of the biological impact of iMSCs on immune cells, explored the applications of iMSCs and iMSC-EVs in diseases, and briefly discussed the fundamental characteristics of EVs. Finally, we overviewed the current advantages and challenges associated with iMSCs and iMSC-EVs. It is our hope that this review related to iMSCs and iMSC-EVs will contribute to the development of new approaches for the treatment of diseases.

The application of proximal tibial anterior closing wedge osteotomy in anterior cruciate ligament reconstruction.

Introduction: Posterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. Methods: Between October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. Results: In a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P < 0.001; the Lysholm score to 88.00 (73.00, 90.50), P < 0.001; and the Tegner score to 8.00 (7.20, 8.05), P = 0.025 at final follow-up. Skin incision healing delays occurred in two instances, yet achieved closure by six weeks. Radiographs at three months demonstrated faster bone healing in oblique osteotomies than transverse ones. Knee joint stability was maintained, with no additional complications or evidence of instability noted. Magnetic resonance imaging (MRI) confirmed graft integrity in all patients, without signs of enlargement or mispositioning at last observation. Conclusion: An augmented PTS angle exceeding 12 may constitute a potential etiology for the failure of ACLR grafts. In such patients, the implementation of ACLR combined with PT-ACWO could mitigate the risk of surgical failure during initial ACLR or subsequent revision procedures.

The cerebellum computes frequency dynamics for motions with numerical precision and cross-individual uniformity.

Cross-individual variability is considered the essence of biology, preventing precise mathematical descriptions of biological motion like the physics law of motion. Here we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in-vivo electrophysiology and optogenetics in mice, we confirmed that deep cerebellar neurons encoded frequencies via populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism was consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform, or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validated the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating-current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for brain-computer interface for motor control.

Mesenchymal stem cells-derived extracellular vesicles ameliorate lupus nephritis by regulating T and B cell responses.

BACKGROUND: Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model. METHODS: The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney. RESULTS: MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney. CONCLUSION: The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.

Effect of Sextant Fixating Angle of Spiral Clavicle Plate on Biomechanical Stability-A Preliminary Finite Element Study.

INTRODUCTION: A spiral clavicle plate has been accepted for its superior multidirectional compatibility in the treatment of midshaft clavicle fractures from a biomechanical perspective. However, the influence of the sextant angle (spiral level) definition on biomechanical performance has not been clarified. A conceptual finite element analysis was conducted to identify the advantages and drawbacks of spiral clavicle plates with various sextant angle definitions. METHODS: Conventional superior and three different conceptual spiral plates with sextant angle definitions ranging from 45 to 135 degrees were constructed to restore an OTA 15-B1.3 midshaft clavicle fracture model. Three major loading scenarios (cantilever downward bending, axial compression, and axial torsion) were simulated to evaluate the reconstructed structural stiffness and the stress on the clavicle plate and bone screws. RESULTS: The spiral clavicle plate demonstrated greater capability in resisting cantilever downward bending with an increase in sextant angle and showed comparable structural stiffness and implant stress compared to the superior clavicle plate. However, weakened resistance to axial compression load was noted for the spiral clavicle plate, with lowered stiffness and increased stress on the clavicle plate and screws as the spiral level increased. CONCLUSION: The spiral clavicle plate has been reported to offer multidirectional compatibility for the treatment of midshaft clavicle fractures, as well as geometric advantages in anatomical matching and reduced skin prominence after surgery. The current study supports that remarkable cantilever bending strength can be achieved with this plate. However, users must consider the potential drawback of lowered axial compression resistance in safety considerations.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

COVID-19 Pandemic on COPD Healthcare Utilization, Exacerbations and Mortality: A Population Study.

RATIONALE: Existing work suggests that patients with COPD (pwCOPD) presented less frequently to the emergency department (ED) and were less likely to be hospitalized during the COVID-19 pandemic but it is unclear if this was due to improved health and disease management or to increased barriers/avoidance of healthcare. The objective of this study is to determine the impact of the pandemic on inpatient and outpatient healthcare utilization, disease incidence, and mortality rates in pwCOPD. METHODS: A retrospective population-based analysis using linked administrative datasets from Alberta, Canada18 months before and after March 12, 2020 was conducted to measure hospitalization, ED and outpatient visits, and COPD outpatient exacerbations during these time periods. Mortality data was also analyzed pre- versus post-pandemic, taking confirmed COVID-19 infection within 30 days into account. Subgroup analysis based on COPD exacerbation risk stratification was undertaken to determine if healthcare utilization differed based on exacerbation risk. Finally, sex-based analysis of healthcare utilization during the pandemic was also completed. RESULTS: Hospitalization/ED visits and outpatient treatment for acute exacerbations of COPD dropped while total outpatient COPD visits, including both virtual and in-person, increased during the pandemic for pwCOPD. Mortality rate increased even after adjusting for COVID-19-associated deaths. Sex-based subgroup analysis showed a greater drop in acute care utilization for females but the rise in mortality was seen for both sexes with men experiencing greater rate of mortality than women. CONCLUSIONS: Overall pwCOPD accessed acute care resources less during the pandemic which may have contributed to a rise in non-COVID all-cause mortality.

4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20. Among these proteins, the upregulated expression of CPT-I was most prominent. CPT-I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial ß-oxidation of fatty acids. Given recent research showing that CPT-I activation could be a viable pathway for NASH treatment, we hypothesized that 35e could serve as a potential agent for treating NASH. The efficacy of 35e in treating NASH was evaluated in methionine- and choline-deficient (MCD) diet- and Western diet (WD)-induced models that mimic human NASH. In the MCD diet-induced model, both short-term (2 weeks) and long-term (7 weeks) treatment with 35e effectively regulated elevated serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of 35e was obtained only in the short-term treatment group. As a comparative compound in the MCD diet-induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride/total cholesterol, serum ALT/AST, or hepatic steatosis. In the WD-induced model, 35e ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that 35e may promote lipid metabolism or impede lipid accumulation. Overall, 35e displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT-I upregulation could further underscore their efficacy as anti-NASH agents.

Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

Enhanced quantum secret sharing protocol for anonymous secure communication utilizing W states.

Quantum secret sharing (QSS) represents the fusion of quantum mechanics principles with secret information sharing, allowing a sender to distribute a secret among receivers for collective recovery. This paper introduces the concept of quantum anonymous secret sharing (QASS) to enhance the practicality of such protocols. We propose a QASS protocol leveraging W states, ensuring both recover-security and anonymity of shared secrets. Our protocol undergoes rigorous evaluation verifying their accuracy and fortifying their security against scenarios involving the active adversary. Additionally, acknowledging the imperfections inherent in real-world communication channels, we conduct a comprehensive analysis of protocol security and efficacy in noisy quantum networks. Our investigations reveal that W states exhibit good performance in mitigating noise interference, making them apt for practical applications.

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin's lymphoma Berlin-Frankfurt-Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% [95% Confidence Interval (CI), 69.0%-83.9%] and 92.3% (95% CI,86.1%-95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5%-95.5%, and 67.9% (95% CI, 55.4%-77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6%-19.0%), 65.7% (95% CI, 47.6%-78.9%), 55.7% (95% CI, 26.2%-77.5%), and 70.7% (95% CI, 48.6%-84.6%), respectively. At the end of follow-up, one of the 5 patients who received maintenance therapy with VBL relapsed, and seven patients receiving ALK inhibitor maintenance therapy did not experience relapse. Conclusion: This study has confirmed the poor prognostic of MDD (+) ，high risk site and SC/LH ,but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Study of chondrogenesis of umbilical cord mesenchymal stem cells in curdlan- poly(vinyl alcohol) composite hydrogels and its mechanical properties of freezing-thawing treatments.

The curdlan gel is a natural material produced by bacteria. It utilizes chemical cross-linking reactions to form a 3D porous composite hydrogel, increasing its porosity and water content, and improving its mechanical properties. It can be used in tissue repair and regenerative medicine. Curdlan-Poly(vinyl alcohol) (PVA) composite hydrogel can rapidly swell within 1 min due to its porous structure. Compression tests confirmed that it still maintains its original mechanical strength, even after five repeated freeze-thaw (FT) processes, making it suitable for long-term cryopreservation. The purpose of this study is to transplant umbilical cord mesenchymal stem cells (UC-MSCs) on Curdlan-PVA composite hydrogel and observe the chondrocytes on the material. The results of using 4',6-diamidino-2-phenylindole (DAPI), hematoxylin and eosin (H&E), calcein-acetoxymethyl ester (calcein AM), and Collagen type II-Fluorescein isothiocyanate (FITC) staining, confirmed that UC-MSCs can attach and differentiate into chondrocytes on 3D Curdlan-PVA composite hydrogel.

Real-world Use and Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada.

OBJECTIVES: Since 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure. METHODS: This retrospective, population-based cohort study identified people with diabetes and heart failure between January 1, 2014, and December 31, 2017, in Alberta, Canada, and followed them for a minimum of 3 years for SGLT2i dispensation and outcomes. Multivariate logistic regression assessed the factors associated with SGTL2i dispensation. Propensity scores were used with regression adjustment to estimate the effect of SGLT2i treatment on heart failure hospitalization. RESULTS: Among 22,025 individuals with diabetes and heart failure (43.4% women, mean age 74.7±11.8 years), only 10.2% were dispensed an SGLT2i. Male sex, age <65 years, a higher baseline glycated hemoglobin, no chronic kidney disease, presence of atherosclerotic cardiovascular disease, and urban residence were associated with SGLT2i dispensation. Lower heart failure hospitalization rates were observed in those with SGLT2i dispensation (548.1 per 100 person-years) vs those without (813.5 per 1,000 person-years; p<0.001) and lower all-cause mortality in those with an SGLT2i than in those without (48.5 per 1,000 person-years vs 206.1 per 1,000 person-years; p<0.001). Regression adjustment found SGLT2i therapy was associated with a 23% reduction in hospitalization. CONCLUSIONS: SGLT2is were dispensed to only 10% of people with diabetes and established heart failure, underscoring a significant care gap. SGLT2i use was associated with a real-world reduction in heart failure hospitalization and all-cause death. This study highlights an important opportunity to optimize SGLT2i use.

Anti-Cancer Effects of CDK4/6 Inhibitor LEE011 and Chemotherapy Drugs on Lymphocytic Leukemia L1210 Cells.

BACKGROUND/AIM: Chronic lymphocytic leukemia is a slowly-progressing disease in which symptoms often do not manifest until years after disease onset. In advanced stages, infection and bleeding are common. Past studies have shown that the interaction between CDK4/6 inhibitors and chemotherapy drugs can enhance the anti-tumor efficacy of drugs and limit toxicity. Therefore, in this study, the treatment effects of combining the CDK4/6 inhibitor LEE011 with chemotherapy drugs bendamustine or hydroxyurea were investigated in vitro. MATERIALS AND METHODS: The mouse lymphocytic leukemia cell line L1210 was treated with LEE011 combined with hydroxyurea or bendamustine. Western blot and flow cytometry were performed to elucidate the mechanisms behind tumor suppression. RESULTS: LEE011 combined with hydroxyurea or bendamustine significantly inhibited proliferation of L1210 cell lines in a concentration- and time-dependent manner as well as increased the arrest of cells in G1 and S phases. The combination of LEE011 with hydroxyurea also reduced the phosphorylation of Rb while increased the expression of total Rb protein. Furthermore, reduced expression of GPX4, which is a key protein in ferroptosis, indicates that the tumor suppression effects of this drug combination could involve ferroptosis. CONCLUSION: CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.

Factors affecting quality of life among patients with corrosive injury.

This study aimed to investigate the factors influencing quality of life (QOL) among patients with corrosive injuries, considering the rising incidence of such cases, particularly in developing countries. Corrosive ingestion is a serious global public health problem and a common form of self-harm. This was a cross-sectional study using purposive sampling. A total of 82 patients with corrosive injuries who were admitted to the gastroenterology ward of a medical center in Taiwan between June 2018 and July 2020 completed the Perceived Stress Scale, Coping Strategy Scale, and World Health Organization Quality of Life Scale. We used an independent t-test and analysis of variance to examine the distribution and differences in demographic and disease characteristics, perceived stress, and the coping strategy scale. Multiple linear regression was then used to analyze the main predictors of QOL. The mean patient age was 58.2 (standard deviation = 2.4) years. A significant difference was observed between patients with a history of mental illness and perceived stress (P < .05). The patients were highly stressed and used emotional coping strategies to solve problems. Stress perception was significantly negatively correlated with overall QOL. Multiple linear regression analysis showed that a history of mental illness was a significant factor for overall QOL. The results of this study suggest that a history of mental illness significantly affects the QOL of patients with corrosive gastrointestinal injuries, and regular assessment and monitoring are essential.

The relationship between kidney disease and mitochondria: a bibliometric study.

BACKGROUND: Due to its highly reabsorptive function, the kidney is a mitochondria-dependent organ. Research on the association between mitochondria and kidney disease has always been a serious focus of researchers, with many publications. Bibliometrics is a secondary analysis of published literature that extracts relevant information to gain insights into hotspots and trends in the field. Through bibliometric analysis, we aimed to understand the development trends and hotspots in the field of research on the association between kidney disease and mitochondria. METHOD: Three bibliometric mapping tools (Biblimetrix R Package, VOS Viewer, CiteSpace) were used to provide an overview of the literature and analyze the co-occurrence of keywords and reference citations. RESULTS: A total of 2672 relevant research articles were included. The co-occurrence network identified three clusters related to the association between mitochondria and kidney disease, including experimental methods, research mechanisms, and disease phenotypes. We found that research in this field has shifted from disease-level studies to mechanism-based studies, with the most prominent disease being diabetic nephropathy and the most prominent pathogenic mechanism being related to mitochondrial ROS production. CONCLUSION: The bibliometric analysis provided a comprehensive understanding of the progress of research on the role of mitochondria in kidney disease, enriching the review literature in this field.

Detecting outliers beyond tolerance limits derived from statistical process control in patient-specific quality assurance.

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.

Research progress on preparation of lateral femoral tunnel and graft fixation in anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) injury is one of the most common types of sports injuries. People's need to participate in sports and desire for a high quality of life promotes the continuous development of ACL reconstruction technology. Arthroscopic ACL reconstruction has been recognized as an effective method for the treatment of ACL injuries. This review analyses and summarizes the advantages and limitations of each surgical procedure for arthroscopic ACL reconstruction reported in the relevant literature so as to promote the future development of more relevant techniques.

Construction of clinical research nurse training program based on position competence.

BACKGROUND: As one of the most important members in clinical trials, the number of clinical research nurses (CRN) can't keep up with the growth of experimental projects, so it is urgent to build clinical research training and strengthen the background knowledge of nurses. AIM: To construct CRN training program based on position competence, accelerate the construction of CRN talent pool, and provide scientific guidance significance for CRN training. METHODS: Based on the position competence model, combined with literature research and qualitative interview results, the first draft was prepared of the CRN training program. Two rounds of correspondence with 16 experts were conducted using the Delphi method to determine the training program. RESULTS: The effective recovery rate of the expert correspondence questionnaire was 100% and the authority coefficients of the 2 rounds of experts were 0.826 and 0.895. Finally, 4 first-level indicators and determine 15 s-level indicators of training objectives. The training program included 4 first-level indicators, training requirements, content, methods, assessment and evaluation, 15 s-level indicators, and 74 third-level indicators. CONCLUSION: The CRN training program based on position competence is scientific and extendable, providing a basis for participation in CRN training.