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Abstract Retinal vein occlusion (RVO) is the leading cause of vision loss due to an obstruction in the retinal venous system. While RVO is often linked to thrombotic tendencies and coagulation abnormalities, the exact role of coagulation traits in its development is not fully understood. This study aims to investigate the potential causal relationship between coagulation traits and the risk of RVO by analyzing publicly available genome-wide association study (GWAS) summary statistics. A two-sample Mendelian randomization (MR) analysis framework was employed to investigate the causal relationship between coagulation traits and the risk of RVO. Stringent quality control measures were applied to select appropriate instrumental variables strongly linked to exposure, such as coagulation factor III (FIII), coagulation factor V (FV), coagulation factor VIII (FVIII), coagulation factor XI (FXI), coagulation factor VII (FVII) and coagulation factor X (FX), as well as plasmin, platelet count, platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW). The study utilized the FinnGen project RVO GWAS summary statistics cohort, consisting of 372 RVO cases and 182,573 controls. The analysis focused on 11 coagulation traits. The research suggests that genetically predicted plasma levels of FIII, FVII, MPV, and PCT may be potentially causative for reducing the risk of RVO, and that levels of FVIII may be potentially causative for increasing the risk of RVO. Our MR analysis, utilizing GWAS data from a comprehensive population-based study, revealed a causal association between plasma levels of FIII, FVII, FVIII, MPV, and PCT with the risk of RVO.

PURPOSE: To investigate the value of dual-energy computed tomography (DECT) in predicting lymphovascular invasion (LVI) and the accuracy of preoperative T-staging of rectal cancer (RC). METHODS: Forty-nine patients with RC who had not received radiotherapy were enrolled to undergo a DECT scan. All patients underwent surgical tumor resection within 3–5 days after the DECT scan. Preoperative T-staging of RC based on images was performed by experienced radiologists. The normalized iodine concentrations (NIC) of the tumor and the perirectal adipose tissue (PAT) from the arterial phase (AP) and venous phase (VP) were measured using DECT. The tumor LVI and T-staging confirmed by pathology were used as the gold standard for grouping (group A, LVI−; group B, LVI+; group C, T1-2; and group D, T3-4a). The NIC values between two groups were compared using the Mann–Whitney U test, with P < 0.05 indicating a statistically significant difference. The accuracy of NIC in predicting LVI and distinguishing T1-2 RC from T3-4a RC were determined via receiver operating characteristic curve analysis, and the optimal cut-off of NIC was determined using the area under the curve. RESULTS: The tumor NIC values were significantly higher in the LV+ group than in the LVI− group in the VP (0.728 ± 0.031 vs. 0.669 ± 0.034, P < 0.001). The NIC values of PAT were significantly higher in the T3-4a group than in the T1-2 group in both the AP (4.034 ± 0.991 vs. 3.115 ± 0.581, P < 0.05) and the VP (5.481 ± 1.054 vs. 3.450 ± 0.980, P < 0.001). The accuracy of using NIC values to distinguish between the LVI+ group and the LVI− group and to diagnose the T3-4a group were 85.7% and 89.8%, respectively. However, there was no statistically significant difference between the NIC value in the LVI+ group and in the LVI− group in the AP. There was also no statistical difference in the tumor NIC value between the T1-2 group and the T3-4a group. CONCLUSION: The tumor and PAT NIC are valuable indicators in RC that can preoperatively predict LVI and improve the accuracy of preoperative RC T-staging. CLINICAL SIGNIFICANCE: The use of DECT improves the T-staging and LVI prediction of RC, which is helpful in guiding the clinical selection of appropriate treatment modalities and improving prognostic outcomes.

Abstract Background Patellar fractures are a common knee injury among elderly patients, with a high risk of developing surgical site infections (SSI) postoperatively, which severely affects patient prognosis and quality of life. Elderly patients are more susceptible to SSI due to various factors such as decreased immune function and chronic diseases. Therefore, identifying the risk factors for SSI is of great clinical significance for prevention. Objective This study aims to analyze the risk factors for postoperative SSI in elderly patients with patellar fractures, providing a basis for developing more effective clinical prevention and treatment strategies. Methods This retrospective study collected data from 856 elderly patients who underwent patellar fracture surgery at Baoding First Central Hospital between January 2017 and December 2023. Patients were divided into SSI and non-SSI groups based on the occurrence of SSI, and their demographic data, comorbidities, and laboratory results were analyzed. Logistic regression was used to identify independent risk factors for SSI, and ROC curve analysis was conducted to determine the optimal cutoff point for predictive indicators. Results The incidence of SSI was found to be 2.1%. Univariate analysis showed that BMI, surgical delay, diabetes, hematocrit (HCT), and albumin (ALB) were significantly associated with SSI. Logistic regression analysis further confirmed that BMI (p = 0.043), surgical delay (p = 0.000), HCT (p = 0.038), ALB (p = 0.015), and diabetes (p = 0.022) were independent risk factors for SSI. ROC curve analysis indicated that the optimal cutoff points for BMI, HCT, and ALB were 25.39 kg/m2, 35.62%, and 39.3 g/L, respectively, with an AUC of 0.794 for the combined predictive indicators. Conclusion High BMI, surgical delay, diabetes, low HCT, and low ALB are independent risk factors for postoperative SSI in elderly patients with patellar fractures. Preoperative management targeting these high-risk factors, such as optimizing patient weight, controlling diabetes, and improving nutritional status, can effectively reduce the incidence of SSI and improve postoperative outcomes. Future multicenter studies may further validate these findings and provide additional prevention strategies.

Matrix metalloproteinases (MMPs), coupled with other proteinases and glycanases, can degrade proteoglycans, collagens, and other extracellular matrix (ECM) components in inflammatory and non-inflammatory arthritis, making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers. For MMP responsiveness, MMP-sensitive peptides (MSPs) are among the most easily synthesized and cost-effective substrates, with free terminal amine and/or carboxyl groups extensively employed in multiple designs. We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis. These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies; acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments; and facilitating cartilage engineering through MMP-mediated degradation, which promotes cell migration, matrix synthesis, and tissue integration. Specifically, the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis (OA), while MSP-based drug carriers for rheumatoid arthritis (RA) can intelligently release anti-inflammatory drugs effectively during flare-ups, or even before symptoms manifest. The continuous progress in MSP development may acceleratedly lead to novel management regimens for arthropathy in the future.

Uncontrolled hemorrhage remains the leading cause of death in clinical and emergency care, posing a major threat to human life. To achieve effective bleeding control, many hemostatic materials have emerged. Among them, nature-derived biopolymers occupy an important position due to the excellent inherent biocompatibility, biodegradability and bioactivity. Additionally, sponges have been widely used in clinical and daily life because of their rapid blood absorption. Therefore, we provide the overview focusing on the latest advances and smart designs of biopolymer-based hemostatic sponge. Starting from the component, the applications of polysaccharide and polypeptide in hemostasis are systematically introduced, and the unique bioactivities such as antibacterial, antioxidant and immunomodulation are also concerned. From the perspective of sponge structure, different preparation processes can obtain unique physical properties and structures, which will affect the material properties such as hemostasis, antibacterial and tissue repair. Notably, as development frontier, the multi-functions of hemostatic materials is summarized, mainly including enhanced coagulation, antibacterial, avoiding tumor recurrence, promoting tissue repair, and hemorrhage monitoring. Finally, the challenges facing the development of biopolymer-based hemostatic sponges are emphasized, and future directions for in vivo biosafety, emerging materials, multiple application scenarios and translational research are proposed.

Introduction: Holistic Approach in Lowering and Tracking Chronic Kidney Disease (HALT-CKD) is a nationwide programme that was introduced in 2017 to combat CKD in Singapore. This study aims to evaluate outcomes of the HALT-CKD programme and identify factors influencing disease progression among early CKD patients. Method: We conducted a retrospective cohort study involving adult patients aged 21 to 80 with CKD stages G1–G3A, recruited from 5 Singapore polyclinics between 2017 and 2018. The primary outcome—time to progression to advanced CKD (G3B–G5)—was tracked until March 2023, based on patients’ last known serum creatinine levels. Descriptive statistics and Cox regression were used. Patients who followed up with other institutions, were deceased or defaulted without developing (or experiencing) the outcome were censored. Results: We studied 3800 patients (mean age: 61.9 years) for a median of 4.7 years. Among them, 12.6% developed advanced CKD despite statistically significant improvements in HbA1c, blood pressure and albuminuria levels. Increasing age, female sex, clinic, baseline creatinine, diastolic blood pressure and HbA1c significantly shortened time to CKD progression. Macro-albuminuria at baseline (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.19–2.61) and at analysis (HR 2.22, 95% CI 1.55–3.19) significantly accelerated advanced CKD progression. Patients who had their angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) dose reduced or discontinued progressed to advanced CKD earlier (HR 1.92, 95% CI 1.50–2.45). Counselling and sodium-glucose cotransporter-2 inhibitor (SGLT2i) use did not significantly delay CKD progression. Conclusion: Maintaining optimal ACEi/ARB dosage is essential to delay CKD progression. Premature cessation or reduction of this dosage should be discouraged. Further research on counselling and SGLT2i use in early CKD is needed to address the growing burden of CKD.

Objective: This study aims to evaluate the effect of noise management in interventional radiology suites on patients undergoing transarterial chemoembolization (TACE). Methods: A retrospective cohort study design was employed. The study included a total of 141 patients with hepatocellular carcinoma who underwent TACE surgery in interventional radiology suite of the First People’s Hospital of Nantong from January 2022 to December 2022. The patients were divided into an observation group (received noise management, n = 70) and a control group (did not receive noise management, n = 71) on the basis of whether they received noise management. Patient demographics and surgical data were collected, and heart rate, blood pressure, and anxiety levels were assessed before, during and after surgery. Satisfaction and the incidence of adverse reactions were also documented. Results: No significant differences were found in general characteristics. The comparison between the observation and control groups revealed statistically significant differences in noise levels (P < 0.001). Additionally, anxiety levels significantly differed between the two groups (P = 0.040) as well as across different time points (P < 0.001). However, no significant difference was found in the occurrence of adverse events between groups (P = 0.772). Furthermore, patient satisfaction was significantly higher in the observation group than that in the control group (P < 0.001). Although no significant differences were found in heart rate and systolic blood pressure between groups (P > 0.05), and a significant main effect of time was observed for both variables (P < 0.001). Conclusion: Noise management in the interventional radiology suite effectively alleviates intraoperative anxiety among patients with TACE and improves treatment satisfaction but has no significant effect on physiological changes and the incidence of adverse events.

Background: Super-elderly patients with choledocholithiasis are considered to be at high risk for undergoing surgery. While laparoscopic transcystic common bile duct exploration (LTCBDE) is regarded as a challenging procedure for super-elderly patients with choledocholithiasis, there have been no reported cases of its use in super-elderly patients over the age of 96. Case summary: This case study presents the case of a 96-year-old female patient with acute calculous cholecystitis and choledocholithiasis. Despite the presence of multiple high-risk comorbidities, the patient underwent with laparoscopic cholecystectomy (LC) plus LTCBDE, with appropriate perioperative safety measures in place, and made a full recovery, being discharged from the hospital on the seventh day following the operation. Conclusion: The case study demonstrates the successful treatment of a 96-year-old patient with choledocholithiasis via LTCBDE, utilising skilled laparoscopic and choledochoscopic techniques along with robust perioperative safety measures. This achievement sets a historical precedent for the successful treatment of a 96-year-old patient with choledocholithiasis via LTCBDE, both domestically and internationally.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for “cell-free therapy” in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

IntroductionTuberculosis (TB) is a serious infectious disease that endangers human health, and TB becomes more difficult in eradiation due to its multidrug resistance (MDR). The objective of this research was to identify novel targets for treating TB.MethodsA 2-fold serial dilution method was used to determine minimal inhibitory concentrations (MIC) of compound M6 against Mycobacterium smegmatis (M. smegmatis). Compound M6 was subjected to reverse molecular docking with seven Mycobacterium tuberculosis proteins, and the best binding protein with the highest LibDock score was evaluated. The target protein with the highest score was purified through prokaryotic expression. Isolated target proteins were investigated for the enzyme activities and for the kinetic effect of compound M6 by absorbance detection. Subsequently, the CRISPR/Cas9 technology was employed to inhibit target gene expression for detecting MIC changes. Finally, potential targets were evaluated for the effect of the compound M6 in bacteria.ResultsThe MIC values of compound M6 against M. smegmatis were 32 μg/mL. The results from reverse molecular docking show that IspD has the highest LibDock score of 142.50, followed by Rv0674, IspF, and Dxr, with docking scores of 110.762, 71.6955, and 57.7446, respectively. IspD is a key enzyme in the 2-C-methyl-D-erythritol 4-phosphate pathway of MTB. The aKi and Ki values of M6 for the substrate MEP are 609.58 μM and 81.33 μM. For CTP, the aKi and Ki values are 657.89 μM and 40.07 μM. With tetracycline inducing CRISPR/Cas9 to suppress the expression of IspD, the MIC value of M6 against IspD went down significantly from 32 μg/mL to 4 μg/mL.ConclusionIspD is a novel target of the compound M6 for treating TB.

Abstract Reprogramming tumor‐associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF‐κB p65, MAPK p38 and JNK by glycolysis‐mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti‐PD‐L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

Purpose To investigate the differences in survival after venous thromboembolism (VTE) and anticoagulation efficacy and safety between catheter (CRVTE) and non-catheter-related VTE (NCRVTE) in cancer patients. Methods A retrospective research was conducted, and consecutive cancer (digestive, respiratory, genitourinary, blood and lymphatic, and the other cancers) patients with VTE were enrolled. The anticoagulation therapies included low-molecular-weight heparin (LMWH), warfarin, new type of direct oral anticoagulants (NDOACs), LMWH combined with warfarin, and LMWH combined with NDOACs. Data were collected from the electronic medical record database of our hospital and were analyzed accordingly by Kruskal-Wallis H Test, Chi-square test, Fisher's exact test, Logistic regressions, Kaplan-Meier analysis, and Cox regressions. Results 263 patients were included, median age in years (interquartile range) was 64(56-71) and 60.5% were male. VTE recurrence rate was 16.7% in CRVTE group which was significantly lower than 34.8% in NCRVTE group ( P = .032). Heart diseases were independently associated with VTE recurrence ( P = .025). Kaplan-Meier survival estimates at 1, 2, and 3 years for CRVTE group were 62.5%, 60.0%, and 47.5%, respectively, compared with 47.9% ( P = .130), 38.7% ( P = .028), and 30.1% ( P = .046), respectively, for NCRVTE group. Cox regression showed surgery ( P = .003), anticoagulation therapy types ( P = .009), VTE types ( P = .006) and cancer types ( P = .039) were independent prognostic factors for 3-year survival after VTE. Nonmajor and major bleeding were not significantly different ( P = .417). Anticoagulation therapy types were independently associated with the bleeding events ( P = .030). Conclusions Cancer patients with CRVTE potentially have a better anticoagulation efficacy and survival compared to NCRVTE, and the anticoagulation safety seems no significant difference.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants and leads to long-term pulmonary complications. The pathogenesis of BPD has not been fully elucidated yet. In recent years, the microbiome and its metabolites, especially short-chain fatty acids (SCFAs), in the gut and lungs have been demonstrated to be involved in the development and progression of the disease. This review aims to summarize the current knowledge on the potential involvement of the microbiome and SCFAs, especially the latter, in the development and progression of BPD. First, we introduce the gut-lung axis, the production and functions of SCFAs, and the role of SCFAs in lung health and diseases. We then discuss the evidence supporting the involvement of the microbiome and SCFAs in BPD. Finally, we elaborate on the potential mechanisms of the microbiome and SCFAs in BPD, including immune modulation, epigenetic regulation, enhancement of barrier function, and modulation of surfactant production and the gut microbiome. This review could advance our understanding of the microbiome and SCFAs in the pathogenesis of BPD, which also helps identify new therapeutic targets and facilitate new drug development.

Abstract The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Abstract Observational studies have found a potential bidirectional positive association between multiple sclerosis and psoriasis, but these studies are susceptible to confounding factors. We examined the directionality of causation using Mendelian randomization and estimated the genetic correlation using the linkage disequilibrium score. We performed Mendelian randomization analysis using large-scale genome-wide association studies datasets from the International Multiple Sclerosis Genetics Consortium (IMSGC, 115,803 individuals of European ancestry) and FinnGen (252,323 individuals of European ancestry). We selected several Mendelian randomization methods including causal analysis using summary effect (CAUSE), inverse variance-weighted (IVW), and pleiotropy-robust methods. According to CAUSE and IVW the genetic liability to MS reduces the risk of psoriasis (CAUSE odds ratio [OR] 0.93, p = 0.045; IVW OR 0.93, p = 2.51 × 10–20), and vice versa (CAUSE OR 0.72, p = 0.001; IVW OR 0.71, p = 4.80 × 10–26). Pleiotropy-robust methods show the same results, with all p-values

Abstract Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p