PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Sodium-glucose exchanger 2 inhibitor canagliflozin promotes mitochondrial metabolism and alleviates salt-induced cardiac hypertrophy via preserving SIRT3 expression.

INTRODUCTION: Excess salt intake is not only an independent risk factor for heart failure, but also one of the most important dietary factors associated with cardiovascular disease worldwide. Metabolic reprogramming in cardiomyocytes is an early event provoking cardiac hypertrophy that leads to subsequent cardiovascular events upon high salt loading. Although SGLT2 inhibitors, such as canagliflozin, displayed impressive cardiovascular health benefits, whether SGLT2 inhibitors protect against cardiac hypertrophy-related metabolic reprogramming upon salt loading remain elusive OBJECTIVES: To investigate whether canagliflozin can improve salt-induced cardiac hypertrophy and the underlying mechanisms. METHODS: Dahl salt-sensitive rats developed cardiac hypertrophy by feeding them an 8% high-salt diet, and some rats were treated with canagliflozin. Cardiac function and structure as well as mitochondrial function were examined. Cardiac proteomics, targeted metabolomics and SIRT3 cardiac-specific knockout mice were used to uncover the underlying mechanisms. RESULTS: In Dahl salt-sensitive rats, canagliflozin showed a potent therapeutic effect on salt-induced cardiac hypertrophy, accompanied by lowered glucose uptake, reduced accumulation of glycolytic end-products and improved cardiac mitochondrial function, which was associated with the recovery of cardiac expression of SIRT3, a key mitochondrial metabolic regulator. Cardiac-specific knockout of SIRT3 not only exacerbated salt-induced cardiac hypertrophy but also abolished the therapeutic effect of canagliflozin. Mechanistically, high salt intake repressed cardiac SIRT3 expression through a calcium-dependent epigenetic modifications, which could be blocked by canagliflozin by inhibiting SGLT1-mediated calcium uptake. SIRT3 improved myocardial metabolic reprogramming by deacetylating MPC1 in cardiomyocytes exposed to pro-hypertrophic stimuli. Similar to canagliflozin, the SIRT3 activator honokiol also exerted therapeutic effects on cardiac hypertrophy. CONCLUSION: Cardiac mitochondrial dysfunction caused by SIRT3 repression is a critical promotional determinant of metabolic pattern switching underlying salt-induced cardiac hypertrophy. Improving SIRT3-mediated mitochondrial function by SGLT2 inhibitors-mediated calcium handling would represent a therapeutic strategy against salt-related cardiovascular events.

Giant magneto-photoluminescence at ultralow field in organic microcrystal arrays for on-chip optical magnetometer.

Optical detection of magnetic field is appealing for integrated photonics; however, the light-matter interaction is usually weak at low field. Here we observe that the photoluminescence (PL) decreases by > 40% at 10 mT in rubrene microcrystals (RMCs) prepared by a capillary-bridge assembly method. The giant magneto-PL (MPL) relies on the singlet-triplet conversion involving triplet-triplet pairs, through the processes of singlet fission (SF) and triplet fusion (TF) during radiative decay. Importantly, the size of RMCs is critical for maximizing MPL as it influences on the photophysical processes of spin state conversion. The SF/TF process is quantified by measuring the prompt/delayed PL with time-resolved spectroscopies, which shows that the geminate SF/TF associated with triplet-triplet pairs are responsible for the giant MPL. Furthermore, the RMC-based magnetometer is constructed on an optical chip, which takes advantages of remarkable low-field sensitivity over a broad range of frequencies, representing a prototype of emerging opto-spintronic molecular devices.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

CD163+ macrophage density in perimysial connective tissue associated with prognosis in IMNM.

OBJECTIVE: The pathological features of immune-mediated necrotizing myopathy (IMNM) are dominated by the infiltration of macrophages. We aimed to perform a histopathologic semiquantitative analysis to investigate the relationship between macrophage markers and prognosis. METHODS: Semiquantitative analysis of histologic features was performed in 62 samples of IMNM. Independent risk factors were identified through univariate and multivariate regression analysis. Cluster analysis was performed using the partitioning around the medoids (PAM) method. Decision tree modeling was utilized to efficiently determine cluster labels for IMNM patients. The validity of the developmental cohort was assessed by accuracy in comparison with the validation cohort. RESULTS: The most enriched groups in patients with IMNM were macrophages expressing CD206 and CD163. In the multivariate logistic regression model, the high density of CD163+ macrophages in perimysial connective tissue increased the risk of unfavorable prognosis (p = 0.025, OR = 1.463, 95% CI: 1.049-2.041). In cluster analysis, patients in Cluster 1, with lower CD163+ macrophage density and inflammatory burden, had a more favorable prognosis. Conversely, patients in Cluster 3, which were enriched for CD163+ macrophages in the perimysial connective tissue, had the most severe clinical features and the worst prognosis. Correlations were found between the density of CD163+ macrophages in connective tissue and symptom duration (R2 = 0.166, p < 0.001), dysphagia (p = 0.004), cardiac involvement (p = 0.021), CK (R2 = 0.067, p = 0.042), CRP (R2 = 0.117, p < 0.001), and ESR (R2 = 0.171, p < 0.001). CONCLUSION: The density of CD163+ macrophages in perimysial connective tissue may serve as a potential marker for the prediction of IMNM prognosis.

[Screw versus Kirschner wire fixation for lateral humeral condyle fractures in children:a meta analysis].

OBJECTIVE: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3. RESULTS: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22, 95%CI(0.09, 0.56), P=0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate(P>0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18, 95%CI(0.05, 0.65), P=0.009]. CONCLUSION: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

[Clinical Features and Prognostic Analysis of Newly Diagnosed Diffuse Large B-cell Lymphoma Combined with Hemophagocytic Syndrome].

OBJECTIVE: To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with and without hemophagocytic syndrome (HPS). METHODS: The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed. The patients were divided into HPS group (15 cases) and non-HPS group (30 cases). The clinical features and prognosis of the two groups were compared, and survival analysis was performed using Kaplan-Meier method. RESULTS: Patients with HSP were mostly characterized by fever, cytopenia and splenomegaly. The levels of ferritin and soluble CD25 increased in all patients. The level of fibrinogen decreased in 66.67% patients, while triglyceride increased in 53.33% patients, and bone marrow hemophagocytosis occurred in 80.00% patients. Compared with non-HSP group, the proportions of patients with advanced stage (Ann Arbor stage III/IV) and lactate dehydrogenase (LDH) ≥240 U/L were higher in HSP group (both P < 0.05). The median survival time of HSP group was 8.0 months, which was significantly shorter than 45.5 months of non-HSP group (P < 0.001). CONCLUSION: The DLBCL patients with HPS have later Ann Arbor stage, higher LDH and shorter overall survival time compared with patients without HPS.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

Group sparse-based Taylor expansion method for liver pharmacokinetic parameters imaging of dynamic fluorescence molecular tomography.

OBJECTIVE: Pharmacokinetic parametric images obtained through dynamic fluorescence molecular tomography (DFMT) has ability of capturing dynamic changes in fluorescence concentration, thereby providing three-dimensional metabolic information for applications in biological research and drug development. However, data processing of DFMT is time-consuming, involves a vast amount of data, and the problem itself is ill-posed, which significantly limits the application of pharmacokinetic parametric images reconstruction. In this study, group sparse-based Taylor expansion (GSTE) method is proposed to address these problems. APPROACH: Firstly, Taylor expansion framework is introduced to reduce time and computational cost. Secondly, group sparsity based on structural prior is introduced to improve reconstruction accuracy. Thirdly, alternating iterative solution based on accelerated gradient descent (AGD) algorithm is introduced to solve the problem. MAIN RESULTS: Numerical simulation and in vivo experimental results demonstrate that, in comparison to existing methods, the proposed approach significantly enhances reconstruction speed without a degradation of quality, particularly when confronted with background fluorescence interference from other organs. SIGNIFICANCE: Our research greatly reduces time and computational cost, providing strong support for real-time monitoring of liver metabolism.

Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

[Ecosystem Service Trade-off Synergy Strength and Spatial Pattern Optimization Based on Bayesian Network： A Case Study of the Fenhe River Basin].

Understanding the strength of trade-off and synergistic relationships among ecosystem services (ESs) is crucial for ecological management and restoration in the Fenhe River Basin. However, there is still a lack of sufficient research on the driving variables and spatial pattern optimization of the strength of ESs relationships in this area. Based on the quantitative assessment of six ESs in the Fenhe River Basin in 2000 and 2020, the ecosystem services trade-off synergy index (TSI) was introduced to quantitatively measure the strength of trade-off and synergistic relationships between each pair of ESs. A Bayesian network was constructed to identify the driving variables of trade-off and synergistic relationships, and sensitivity analysis was conducted to determine the degree of influence of key variables on the strength of these relationships. The optimization area of the strength of ESs trade-off and synergistic relationships was characterized in spatial patterns. The results showed that:① There were significant spatiotemporal differences in the six ESs in the Fenhe River Basin in 2000 and 2020. In terms of time scale, water yield, net primary productivity, crop productivity, soil conservation, and carbon storage all showed a trend of fluctuating increase. In terms of spatial scale, the spatial distribution changes in the six ESs were relatively small over the 20 years. ② The TSI of carbon storage was high in the surrounding area and low in the middle, showing a four-high and four-low pattern. The areas with the highest TSI between grain supply and other services were distributed from north to south. ③ Sensitivity analysis found that the strength of water yield, soil conservation, and habitat quality were significantly affected by precipitation, plant root depth restriction, and rainfall erosion. According to the conditional probability of different states of key variables, Wenshui County, Qingxu County, and Qi County in the central part of the Fenhe River Basin were identified as high-value areas for trade-off and synergistic relationships, which could be used as key areas for ecological restoration. These findings have important theoretical and practical significance for understanding the complex relationship between multiple ESs trade-off and synergistic relationships and their driving variables and for proposing sustainable ecological environment management policies.

Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole-calcifuge behaviors of three Camellia species.

We grew three yellow Camellia species (the calcifuge C. nitidissima and C. tunghinensis, and the calcicole C. pubipetala) in acidic and calcareous soils for 7 months and assessed their photosynthetic physiological characteristics, growth performance, and element concentrations in this developmental context. The calcifuge C. nitidissima and C. tunghinensis species exhibited poor growth with leaf chlorosis, growth stagnation, and root disintegration in calcareous soils, and with their P n, G s, T r, F v/F m, ΦPSII, ETR, qP, leaf Chla, Chlb, and Chl(a + b) concentrations, and root, stem, leaf, and total biomass being significantly lower when grown in calcareous soils relative to in acidic soils. In contrast, the calcicole C. pubipetala grew well in both acidic and calcareous soils, with few differences in the above parameters between these two soil substrates. The absorption and/or transportation of nutrient elements such as N, K, Ca, Mg, and Fe by the two calcifuge Camellia species plants grown in calcareous soils were restrained. Soil type plays a major role in the failure of the two calcifuge Camellia species to establish themselves in calcareous soils, whereas other factors such as competition and human activity are likely more important limiting factors in the reverse case. This study furthers our understanding of the factors influencing the distribution of these rare and endangered yellow Camellia species, allowing for improved management of these species in conservation projects and horticultural production.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and ß-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Tunable abundant valley Hall effect and chiral spin-valley locking in Janus monolayer VCGeN4.

It is both conceptually and practically fascinating to explore fundamental research studies and practical applications of two-dimensional systems with the tunable abundant valley Hall effect. In this work, based on first-principles calculations, the tunable abundant valley Hall effect is proved to appear in Janus monolayer VCGeN4. When the magnetization is along the out-of-plane direction, VCGeN4 is an intrinsic ferromagnetic semiconductor with a valley feature. The intriguing spontaneous valley polarization exists in VCGeN4 due to the common influence of broken inversion and time-reversal symmetries, which makes it easier to realize the anomalous valley Hall effect. Furthermore, we observe that the valley-non-equilibrium quantum anomalous Hall effect is driven by external strain, which is located between two half-valley-metal states. When reversing the magnetization, the spin flipping makes the position of the edge state to change from one valley to another valley, demonstrating an intriguing behavior known as chiral spin-valley locking. Although the easy magnetic axis orientation is along the in-plane direction, we can utilize an external magnetic field to transform the magnetic axis orientation. Moreover, it is found that the valley state, electronic and magnetic properties can be well regulated by the electric field. Our works explore the mechanism of the tunable abundant valley Hall effect by applying an external strain and electric field, which provides a perfect platform to investigate the spin, valley, and topology.

Prevalence of cigarette use and addiction among Chinese females by age and province: Findings from nationwide China Health Literacy Survey during 2018-19.

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.

[Meta-analysis of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures].

OBJECTIVE: To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis. METHODS: Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software. RESULTS: Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [MD=-16.79,95%CI(-25.72,-7.85),P=0.000 2] and blood loss[MD=-70.49,95%CI(-79.34,-61.65),P<0.000 01] between two groups had statistically differences,while joint depression[MD=-0.17,95%CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74, 95%CI(0.35,1.57),P=0.43],infection rate [RR=1.21,95%CI(0.31,4.70),P=0.78] between two groups had no differences. CONCLUSION: The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

The perilous consequences of bowel preparation: a case study with literature review of Boerhaave syndrome.

Colonoscopy is widely acknowledged as a prevalent and efficacious approach for the diagnosis and treatment of gastrointestinal disorders. In order to guarantee an effective colonoscopy, it is imperative for patients to undergo an optimal bowel preparation regimen. This entails the consumption of a substantial volume of a non-absorbable solution to comprehensively purge the colon of any fecal residue. Nevertheless, it is noteworthy to acknowledge that the bowel preparation procedure may occasionally elicit adverse symptoms such as nausea and vomiting. In exceptional instances, the occurrence of excessive vomiting may lead to the rupture of the distal esophagus, a grave medical condition referred to as Boerhaave syndrome (BS). Timely identification and efficient intervention are imperative for the management of this infrequent yet potentially perilous ailment. This investigation presents a case study of a patient who developed BS subsequent to the ingestion of mannitol during bowel preparation. Furthermore, an exhaustive examination of extant case reports and pertinent literature on esophageal perforation linked to colonoscopy has been conducted. This analysis provides valuable insights into the prevention, reduction, and treatment of such serious complications.

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity.

Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed by M. smegmatis against COG1410 involving ClpC. Upon subjecting M. smegmatis to serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.

Low-dose radiotherapy synergizes with iRGD-antiCD3-modified T cells by facilitating T cell infiltration.

BACKGROUND AND PURPOSE: Poor penetration of transferred T cells represents a critical factor impeding the development of adoptive cell therapy in solid tumors. We demonstrated that iRGD-antiCD3 modification promoted both T cell infiltration and activation in our previous work. Interest in low-dose radiotherapy has recently been renewed due to its immuno-stimulatory effects including T cell recruitment. This study aims to explore the synergistic effects between low-dose radiotherapy and iRGD-antiCD3-modified T cells. MATERIALS AND METHODS: Flow cytometry was performed to assess the expression of iRGD receptors and chemokines. T cell infiltration was evaluated by immunohistofluorescence and in vivo real-time fluorescence imaging and antitumor effects were investigated by in vivo bioluminescence imaging in the gastric cancer peritoneal metastasis mouse model. RESULTS: We found that 2 Gy irradiation upregulated the expression of all three iRGD receptors and T-cell chemokines. The addition of 2 Gy low-dose irradiation boosted the accumulation and penetration of iRGD-antiCD3-modified T cells in peritoneal tumor nodules. Combining 2 Gy low-dose irradiation with iRGD-antiCD3-modified T cells significantly inhibited tumor growth and prolonged survival in the peritoneal metastasis mouse model with a favorable safety profile. CONCLUSION: Altogether, we demonstrated that low-dose radiotherapy could improve the antitumor potency of iRGD-antiCD3-modified T cells by promoting T cell infiltration, providing a rationale for exploring low-dose radiotherapy in combination of other adoptive T cell therapies in solid tumors.