Physeal-Sparing, All-Inside Anterior Cruciate Ligament Reconstruction Using Quadrupled Semitendinosus Autograft and Suture Tape Augmentation for Skeletally Immature Patients.

The anterior cruciate ligament (ACL) is the primary soft-tissue structure for anterior stabilization of the knee and is one of the most frequently injured structures. The incidence of ACL injuries in children and adolescents ranges from 92 to 151 per 100,000 person-years. The choice of surgical treatment for this population group is controversial, with a widespread concern that adult reconstruction techniques may damage the epiphyseal plate, compromise growth, or cause deformity. In this article, we describe a physeal-sparing, all-inside ACL reconstruction technique for skeletally immature patients. This technique is supported by retrograde drilling of the femoral tunnel and retrograde drilling of the tibial tunnel, both of which are able to avoid the epiphyseal growth line. Fixation of the quadrupled semitendinosus autograft and suture tape augmentation are achieved by soft-tissue buttons on the femur and tibia. The surgical details of this reproducible reconstruction technique are elaborated.

Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex.

Chronic pain is a complex disease. It seriously affects patients' quality of life and imposes a significant economic burden on society. Santacruzamate A (SCA) is a natural product isolated from marine cyanobacteria in Panama. In this study, we first demonstrated that SCA could alleviate chronic inflammatory pain, pain-related anxiety, and depression emotions induced by complete Freund's adjuvant in mice while inhibiting microglial activation in the anterior cingulate cortex. Moreover, SCA treatment attenuated lipopolysaccharide (LPS)-induced inflammatory response by downregulating interleukin 1ß and 6 (IL-1ß and IL-6) and tumor necrosis factor-α (TNF-α) levels in BV2 cells. Furthermore, we found that SCA could bind to soluble epoxide hydrolase (sEH) through molecular docking technology, and the thermal stability of sEH was enhanced after binding of SCA to the sEH protein. Meanwhile, we identified that SCA could reduce the sEH enzyme activity and inhibit sEH protein overexpression in the LPS stimulation model. The results indicated that SCA could alleviate the development of inflammation by inhibiting the enzyme activity and expression of sEH to further reduce chronic inflammatory pain. Our study suggested that SCA could be a potential drug for treating chronic inflammatory pain.

Ectopic Reconstitution of a Spine-Apparatus Like Structure Provides Insight into Mechanisms Underlying Its Formation.

The endoplasmic reticulum (ER) is a continuous cellular endomembrane network that displays focal specializations. Most notable examples of such specializations include the spine apparatus of neuronal dendrites, and the cisternal organelle of axonal initial segments. Both organelles exhibit stacks of smooth ER sheets with a narrow lumen and interconnected by a dense protein matrix. The actin-binding protein synaptopodin is required for their formation. Here, we report that expression in non-neuronal cells of a synaptopodin construct targeted to the ER is sufficient to generate stacked ER cisterns resembling the spine apparatus with molecular properties distinct from the surrounding ER. Cisterns within these stacks are connected to each other by an actin-based matrix that contains proteins also found at the spine apparatus of neuronal spines. These findings reveal a critical role of a synaptopodin-dependent actin matrix in generating cis-ternal stacks. These ectopically generated structures provide insight into spine apparatus morphogenesis.

Similar outcomes between arthroscopic capsular release and manipulation under anaesthesia for frozen shoulder: A meta-analysis.

To compared the arthroscopic capsular release (ACR) with manipulation under anaesthesia (MUA) for the surgical treatment of frozen shoulder (FS) based on postoperative outcomes and complications. PubMed, Cochrane Library, Embase, and Web of Science were searched on October 2, 2023 to retrieve eligible studies that compared ACR with MUA in terms of clinical outcomes (pain visual analogue scale, external rotation, forward flexion and adverse events) for patients with FS. Mean differences (MD) were calculated for continuous outcomes and odds ratios (OR) were calculated for dichotomous outcomes. Six papers, including 5 clinical studies (a total of 690 shoulders), were included in the final meta-analysis. The forward flexion was found to be larger in the ACR group at 3 months (MD, 2.73; 95%CI, 0.42-5.04; I2 = 44%; P = 0.02) and 6 months (MD, 2.36; 95%CI, 1.29-3.44; I2 = 0%; P < 0.0001). Except for this, ACR was comparable with MUA in terms of pain visual analogue scale at 3, 6 and 12 months (p = 0.25, p = 0.11, p = 0.28, respectively), external rotation at 3, 6 and 12 months (p = 0.15, p = 0.52, p = 0.23, respectively), and forward flexion at 12 months (p = 0.08). There were no differences in complication rates between the two groups (OR, 0.82; 95%CI, 0.47-1.44; I2 = 0%; P = 0.50). In comparison with MUA, ACR demonstrated better outcomes for forward flexion at 3 and 6 months, while there were no significant differences between ACR and MUA in terms of pain visual analogue scale, external rotation and adverse events.

Long-term effects of exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear: A meta-analysis of randomized controlled trials.

BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression. RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods. CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.

Appropriate thromboprophylaxis strategy for COVID-19 patients on dosage, antiplatelet therapy, outpatient and post-discharge prophylaxis: a meta-analysis of randomized controlled trials.

BACKGROUND: There was controversy surrounding the optimal thromboprophylaxis strategy for COVID-19 patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and post-discharge. To explore this, we performed a meta-analysis of randomized controlled trials. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet and post-discharge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. RESULTS: Our study included a total of 25 randomized controlled trials, involving 17,911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95%CI, 0.45 to 0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For non-critically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95%CI 0.34 to 0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95%CI 1.22 to 3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95%CI 0.21 to 0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For post-discharge patients, post-discharge prophylaxis reduced thromboembolism risk (RR, 0.49; 95%CI 0.31 to 0.76) but increased major bleeding risk (RR, 2.63; 95%CI, 1.13 to 6.14). CONCLUSION: For non-critically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and post-discharge patients, required further investigation and confirmation through rigorous evidence studies.

A Case Report of Consecutive Live Birth Twice Through in vitro Fertilization and Embryo Transfer After Endometrial Carcinoma Fertility Preservation Treatment.

Preserving fertility is a vital concern for young women diagnosed with endometrial carcinoma. The clinical management of such patients is often disappointing. It is rare to have two consecutive successful pregnancies. We present a child-bearing-age woman who underwent fertility preservation therapy due to endometrial carcinoma. Following fertility preservation therapy, she underwent in vitro fertilization and embryo transfer. After receiving her first fresh embryo transfer, she successfully conceived and gave birth to a healthy child. Two years after the first embryo transfer and regular follow-up, she had another frozen embryo transfer of two cleavage embryos and successfully gave birth to another healthy baby. After the delivery of her second child, she underwent surgical treatment for endometrial carcinoma. For endometrial carcinoma patients who intend to preserve fertility, high-quality long-term follow-up and personalized treatment are necessary.

In this case report, we share the story of one young woman who had endometrial cancer but desired to have children. She received fertility-sparing treatment and in vitro fertilization to increase her chances of conceiving. She successfully delivered a healthy child after the first embryo transfer. Two years later, she had another healthy child through a second frozen embryo transfer. Rigorous monitoring showed no cancer recurrence throughout the entire treatment. There are currently few reported cases of a patient with endometrial cancer successfully and safely giving birth twice through assisted reproductive technology. This case report emphasizes that, with personalized treatment and monitoring, endometrial cancer patients can have multiple pregnancies safely. In summary, this case report brings hope to young women with early-stage endometrial cancer who aspire to become mothers. With the right support, they can overcome the challenges of cancer and have their own babies.

Preferences in anterior cruciate ligament reconstruction: A survey among orthopedic surgeons in China.

The purpose of this study was to reveal the current trends and preferences of Chinese orthopedic surgeons regarding anterior cruciate ligament (ACL) reconstruction through a nationwide web-based survey conducted in China. The survey questionnaire was distributed via WeChat to the chairmen of provincial orthopedic and sports medicine organizing committees in China, who then shared it in their respective WeChat workgroups. The questionnaire consisted of 52 multiple-choice questions covering 8 sections. Data collection was implemented by Questionnaire Star. A total of 812 valid questionnaires were returned: 94.21% of the respondents preferred single-bundle reconstruction of ACL, while 61.70% preferred autogenous semitendinosus plus gracilis reconstruction; 76.35% of the respondents preferred establishing the femoral tunnel first, while 47.29% preferred establishing the femoral tunnel through a medial auxiliary approach; and 85.10% of the respondents recommended patients to undergo surgery within 3 months after ligament injury. Besides, the vast majority of respondents chose to retain the ligamentous remnant bundle (92.98%) and recommended routine use of knee braces postoperatively (94.09%). It is recommended to perform arthroscopic single-bundle ACL reconstruction with the remnant preserving technique using a hamstring autograft within 3 months of ACL rupture, with support of postoperative functional braces.

Interposition Grafting Using Fascia Lata Autograft for Failed Rotator Cuff Repairs.

Massive rotator cuff tears are a huge challenge for orthopaedic surgeons, as the patients may be in need of multiple operations, even including reverse total shoulder arthroplasty. The various repair methods for the rotator cuff, such as partial rotator cuff repair, patch-augmented rotator cuff repair, bridging rotator cuff reconstruction with graft interposition, tendon transfer, and superior capsular reconstruction, have always been the focus of research. During surgical intervention for failed rotator cuff repairs, complexity of tears, poor tissue quality, retained hardware, and adhesions are the problems routinely encountered. In this Technical Note, we describe the technique of interposition grafting using fascia lata autograft to reconstruct the rotator cuff after failed primary repair.

Economic burden attributable to healthcare-associated infections at western China hospitals: 6 Year, prospective cohort study.

OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.

TOM40 mediates the effect of TSPO on postpartum depression partially through regulating calcium homeostasis in microglia.

AIMS: To assess the effect of the translocator protein 18 kDa (TSPO) on postpartum depression and explore its mechanism. METHODS: Postpartum depression (PPD) mouse model was established, and flow cytometry, immunofluorescence, Western blot analysis, real-time quantitative PCR, adeno-associated virus (AAV), co-immunoprecipitation-mass spectrometry and immunofluorescence co-staining were used to detect the effect of TSPO ligand ZBD-2 on PPD mice. RESULTS: ZBD-2 inhibits the overactivation of microglia in the hippocampus and amygdala of PPD model mice. ZBD-2 not only inhibited the inflammation but also repressed the burst of reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Meanwhile, ZBD-2 protects mitochondria from LPS-induced damages through inhibiting the influx of calcium. ZBD-2 modulated the calcium influx by increasing the level of translocase of the outer mitochondrial membrane 40 (TOM40) and reducing the interaction of TSPO and TOM40. In addition, the effect of ZBD-2 was partially dependent on anti-oxidative process. Knockdown of TOM40 by adeno-associated virus (AAV) in the hippocampus or amygdala dramatically reduced the effect of ZBD-2 on PPD, indicating that TOM40 mediates the effect of ZBD-2 on PPD. CONCLUSIONS: TOM40 is required for the effect of ZBD-2 on treating anxiety and depression in PPD mice. This study reveals the role of microglia TSPO in PPD development and provides the new therapeutic strategy for PPD.

How to predict the dimensions of anterior cruciate ligament in children based on MRI?

There are many studies examining the dimensions of the anterior cruciate ligament (ACL) in children. The correlations between the ACL size in children and other parameters are not well understood. To detect the correlations between the ACL size in children and other parameters including age, gender, bone and soft tissue parameters through measurements on MRI images, and to establish prediction models for the ACL size. A total of 99 patients who underwent MRI scan were included (39 girls, 60 boys; mean age, 13.01 ±â€…3.94; range of age, 4 to 18). The following measurements were taken on MRI images by 2 observers: ACL length, ACL width, posterior cruciate ligament (PCL) length, the distance from the most anterior aspect of the tibial epiphysis to the anterior aspect of the ACL tibial insertion (AATI), the distance from the most anterior aspect of the tibial epiphysis to the posterior aspect of the ACL tibial insertion (APTI), and the tibial anteroposterior diameter (AP). Correlations between these measurements and the patients' gender and age were investigated, and univariate and multiple linear regression models were established accordingly. Before 13 years old, the ACL length was significantly correlated with the tibial anteroposterior diameter and age (R2 = 0.872, P < .001), and there were no statistically significant gender differences. After 13 years old, the ACL length was significantly correlated with the PCL length and APTI in males (R2 = 0.443, P < .001), and with the PCL length in females (R2 = 0.443, P < .001). In children under 13 years old, there was no significant gender difference in ACL length, and the tibial anteroposterior diameter and age were found to be important indicators in assessing the ACL size. After 13 years old, a significant gender difference in ACL length was observed, and the ACL length was found to be weakly correlated with age and bone parameters. In order to accurately evaluate the ACL size in children aged 13 years and above, it is necessary to refer to the dimensions of the ACL on the collateral side.

Features of the immunosuppressive tumor microenvironment in endometrial cancer based on molecular subtype.

Endometrial cancer (EC) is one of the three most prevalent gynecological tumors affecting women and is the most prevalent gynecological malignancy in the developed world. Its incidence is rapidly increasing worldwide, mostly affecting postmenopausal women, whereas recently its prevalence has increased in younger people. EC is an immune gene disease and many studies have shown that the tumor-immunosuppressive microenvironment plays an important role in cancer progression. In recent years, findings regarding the immunosuppressive tumor microenvironment (ITME) of EC have included immune evasion mechanisms and immunotherapy, which are mostly immune checkpoint inhibitors (ICI) for EC. Recently studies on the ITME of different molecular types of EC have found that different molecular types may have different ITME. With the research on the immune microenvironment of EC, a new immunophenotype classification based on the immune microenvironment has been carried out in recent years. However, the impact of the ITME on EC remains unclear, and the immunophenotype of EC remains limited to the research stage. Our review describes recent findings regarding the ITME features of different EC molecular types. The advent of immunotherapy has brought hope for improved efficacy and prognosis in patients with advanced or recurrent EC. The efficacy and safety of ICIs combination therapy remains the focus of future research.

Reliability of the Tibial Spine Versus ACL Stump in Assisting Tibial Tunnel Positioning During ACL Reconstruction: Analysis Based on 3-Dimensional Computed Tomography Modeling.

Background: Several techniques have been used by surgeons for anatomic tibial tunnel placement in anterior cruciate ligament (ACL) reconstruction, including the ACL stump positioning (ASP) technique and the tibial spine positioning (TSP) technique. Purpose/Hypothesis: The purpose of this study was to evaluate whether bony landmarks (medial and lateral tibial spine [MLTS]) can be a reliable reference for improving the accuracy of tibial tunnel placement in anatomic single-bundle ACL reconstruction compared with the ACL stump. It was hypothesized that the MLTS would not be a reliable bony landmark for tibial tunnel placement. Study Design: Cohort study; Level of evidence, 3. Methods: The 3-dimensional computed tomography images of 111 patients who underwent ACL reconstruction between 2020 and 2021 were included in this study. For tibial tunnel placement, the ASP technique was used in 49 patients, and the TSP technique was used in 62 patients. The 3-dimensional computed tomography images were reconstructed to enable measurements of the locations of the MLTS and tunnel center based on a grid method. Statistical analysis was conducted to compare the MLTS location and tibial tunnel position as well as the accuracy (mean distance of each actual location from the anatomic center) and precision (standard deviation of the accuracy, indicating the reproducibility of the tunnel position) of the tunnel position between the ASP and TSP groups. Results: Significant differences were observed between the ASP and TSP groups in terms of the tibial tunnel position on the mediolateral axis (46.7% ± 2.0% vs 45.9% ± 2.2%, respectively; P = .034), while no significant differences were found in terms of the accuracy (4.1% vs 4.6%, respectively; P = .259) or precision (2.1% vs 2.1%, respectively; P = .259) of tibial tunnel positioning between the 2 groups. Conclusion: In anatomic single-bundle ACL reconstruction, the use of the MLTS for tibial tunnel placement achieved comparable accuracy and precision compared with the use of ACL remnants, supporting its role as a reliable bony landmark in tibial tunnel positioning.

Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons.

Synaptojanin-1 (SJ1) is a major neuronal-enriched PI(4,5)P2 4- and 5-phosphatase implicated in the shedding of endocytic factors during endocytosis. A mutation (R258Q) that impairs selectively its 4-phosphatase activity causes Parkinsonism in humans and neurological defects in mice (SJ1RQKI mice). Studies of these mice showed, besides an abnormal assembly state of endocytic factors at synapses, the presence of dystrophic nerve terminals selectively in a subset of nigro-striatal dopamine (DA)-ergic axons, suggesting a special lability of DA neurons to the impairment of SJ1 function. Here we have further investigated the impact of SJ1 on DA neurons using iPSC-derived SJ1 KO and SJ1RQKI DA neurons and their isogenic controls. In addition to the expected enhanced clustering of endocytic factors in nerve terminals, we observed in both SJ1 mutant neuronal lines increased cilia length. Further analysis of cilia of SJ1RQDA neurons revealed abnormal accumulation of the Ca2+ channel Cav1.3 and of ubiquitin chains, suggesting an impaired clearing of proteins from cilia which may result from an endocytic defect at the ciliary base, where a focal concentration of SJ1 was observed. We suggest that SJ1 may contribute to the control of ciliary protein dynamics in DA neurons, with implications on cilia-mediated signaling.

Membrane remodeling properties of the Parkinson's disease protein LRRK2.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson's disease. LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell-free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low-curvature liposomes into narrow tubules in a guanylnucleotide-dependent but Adenosine 5'-triphosphate-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.

Relationship between the Ratio of Red Cell Distribution Width to Albumin and 28-Day Mortality among Chinese Patients over 80 Years with Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a prevalent heart arrhythmia in elderly adults aged 80 years or older. The red cell distribution width (RDW) to albumin ratio has been acknowledged as a reliable prognostic marker for poor outcomes in a variety of disorders. However, there exists limited scientific evidence on the association of RDW to albumin (RAR) with mortality in geriatric individuals with AF. METHODS: From January 2015 to June 2020, a retrospective study was conducted in a tertiary academic institution that diagnosed 1,141 elderly adults with AF. The RAR value was calculated as the ratio of RDW (%) to albumin (g/dL). The potential association between RAR and cardiovascular mortality and the risk of all-cause mortality within 28 days was evaluated by means of multivariable Cox regression analysis. RESULTS: The 28-day all-cause and cardiovascular mortality rates were 8.7% and 3.3%, respectively. Increased RAR tertiles were found to be significantly associated with greater all-cause mortality (T1: 1.6%; T2: 6.2%; T3: 18.1%, p < 0.001) and cardiovascular mortality (T1: 0.8%; T2: 2.9%; T3: 6.3%, p < 0.001) using Kaplan-Meier analysis. Continuous RAR had a positive association with all-cause mortality (hazard ratios [HR] = 1.42, 95% confidence interval [CI] 1.23-1.65) and cardiovascular mortality (HR = 1.31, 95% CI: 1.05-1.64), even after accounting for numerous confounding variables. In comparison to the T1 group, individuals with the highest RAR levels displayed a greater risk of all-cause mortality (HR = 2.73, 95% CI: 1.11-6.74) and cardiovascular mortality (HR = 2.59, 95% CI: 0.69-9.78). Increased RAR levels were related to higher rates of cardiovascular and all-cause mortality across almost all subgroups. CONCLUSION: RAR is independently correlated with 28-day all-cause mortality and cardiovascular mortality in AF-affected individuals aged ≥80.

The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D (VitD) has been shown to be important for the immune response of the respiratory system, but the preventive and therapeutic effects of vitamin D supplementation on SARS-CoV-2 infection are controversial. This study aimed to determine the role of vitamin D supplementation in the prevention and treatment of SARS-CoV-2 infection through a meta-analysis of randomized controlled trials. METHODS: The databases of PubMed, Cochrane Library, Embase, Web of Science and Google Scholar were searched systematically from inception to April 17,2023 to identify trials involving a randomized comparison of vitamin D supplementation versus non-vitamin D supplementation for SARS-CoV-2 infection prevention or treatment. RESULTS: We retrieved 25 eligible trials, including 8128 participants. Four trials compared the preventive effects of vitamin D supplementation on SARS-CoV-2 infection, and the results (RR 0.31; 95%CI 0.07 to 1.32) were inconclusive. Regarding the treatment of SARS-CoV-2 infection with vitamin D supplementation, it was found that vitamin D supplementation could significantly reduce the rates of ICU admission (RR 0.63; 95%CI 0.44 to 0.89) and mechanical ventilation (RR 0.58; 95%CI 0.39 to 0.84), but had no statistically significant effect on mortality. However, in subgroup analyses based on the patients' specific conditions, vitamin D supplementation significantly reduced the mortality in patients with vitamin D deficiency (RR 0.76; 95%CI 0.58 to 0.98). CONCLUSION: Vitamin D supplementation may have some beneficial impact on the severity of illness caused by SARS-CoV-2, particularly in VitD deficient patients, but further studies are still needed.

Altered expression of the L-arginine/nitric oxide pathway in ovarian cancer: metabolic biomarkers and biological implications.

MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). RESULTS: Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. CONCLUSION: Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.

BACKGROUND: Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome. METHODS: We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases. RESULTS: Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized. CONCLUSION: This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.