Replication Stress Induces ATR/CHK1-Dependent Nonrandom Segregation of Damaged Chromosomes.

Nonrandom DNA segregation (NDS) is a mitotic event in which sister chromatids carrying the oldest DNA strands are inherited exclusively by one of the two daughter cells. Although this phenomenon has been observed across various organisms, the mechanism and physiological relevance of this event remain poorly defined. Here, we demonstrate that DNA replication stress can trigger NDS in human cells. This biased inheritance of old template DNA is associated with the asymmetric DNA damage response (DDR), which derives at least in part from telomeric DNA. Mechanistically, we reveal that the ATR/CHK1 signaling pathway plays an essential role in mediating NDS. We show that this biased segregation process leads to cell-cycle arrest and cell death in damaged daughter cells inheriting newly replicated DNA. These data therefore identify a key role for NDS in the maintenance of genomic integrity within cancer cell populations undergoing replication stress due to oncogene activation.

Variation in Avian Predation Pressure as a Driver for the Diversification of Periodical Cicada Broods.

AbstractPeriodical cicadas live 13 or 17 years underground as nymphs, then emerge in synchrony as adults to reproduce. Developmentally synchronized populations called broods rarely coexist, with one dominant brood locally excluding those that emerge in off years. Twelve modern 17-year cicada broods are believed to have descended from only three ancestral broods following the last glaciation. The mechanisms by which these daughter broods overcame exclusion by the ancestral brood to synchronously emerge in a different year, however, are elusive. Here, we demonstrate that temporal variation in the population density of generalist predators can allow intermittent opportunities for new broods to invade, even though a single brood remains dominant most of the time. We show that this mechanism is consistent, in terms of the type and frequency of brood replacements, with the distribution of periodical cicada broods throughout North America today. Although we investigate one particularly charismatic case study, the mechanisms involved (competitive exclusion, Allee effects, trait variation, predation, and temporal variability) are ubiquitous and could contribute to patterns of species diversity in a range of systems.

Hybrid Membrane of Sulfonated Poly(aryl ether ketone sulfone) Modified by Molybdenum Clusters with Enhanced Proton Conductivity.

Developing novel proton exchange membranes (PEMs) with low cost and superior performance to replace Nafion is of great significance. Polyoxometalate-doped sulfonated poly(aryl ether ketone sulfone) (SPAEKS) allows for the amalgamation of the advantages in each constituent, thereby achieving an optimized performance for the hybrid PEMs. Herein, the hybrid membranes by introducing 2MeIm-{Mo132} into SPAEKS are obtained. Excellent hydrophilic properties of 2MeIm-{Mo132} can help more water molecules be retained in the hybrid membrane, providing abundant carriers for proton transport and proton hopping sites to build successive hydrophilic channels, thus lowering the energy barrier, accelerating the proton migration, and significantly fostering the proton conductivity of hybrid membranes. Especially, SP-2MIMo132-5 exhibits an enhanced proton conductivity of 75 mS cm-1 at 80 °C, which is 82.9% higher than pristine SPAEKS membrane. Additionally, this membrane is suitable for application in proton exchange membrane fuel cells, and a maximum power density of 266.2 mW cm-2 can be achieved at 80 °C, which far exceeds that of pristine SPAEKS membrane (54.6 mW cm-2). This work demonstrates that polyoxometalate-based clusters can serve as excellent proton conduction sites, opening up the choice of proton conduction carriers in hybrid membrane design and providing a novel idea to manufacture high-performance PEMs.

Genomic characterization and related functional genes of γ- poly glutamic acid producing Bacillus subtilis.

γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in various fields, including food, biomedical and environmental fields. In this study, we screened natto samples for two strains of Bacillus subtilis N3378-2at and N3378-3At that produce γ-PGA. We then identified the γ-PGA synthetase gene cluster (PgsB, PgsC, PgsA, YwtC and PgdS), glutamate racemase RacE, phage-derived γ-PGA hydrolase (PghB and PghC) and exo-γ-glutamyl peptidase (GGT) from the genome of these strains. Based on these γ-PGA-related protein sequences from isolated Bacillus subtilis and 181 B. subtilis obtained from GenBank, we carried out genotyping analysis and classified them into types 1-5. Since we found B. amyloliquefaciens LL3 can produce γ-PGA, we obtained the B. velezensis and B. amyloliquefaciens strains from GenBank and classified them into types 6 and 7 based on LL3. Finally, we constructed evolutionary trees for these protein sequences. This study analyzed the distribution of γ-PGA-related protein sequences in the genomes of B. subtilis, B. velezensis and B. amyloliquefaciens strains, then the evolutionary diversity of these protein sequences was analyzed, which provided novel information for the development and utilization of γ-PGA-producing strains.

Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome.

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

Comparison of trait and state mind wandering among schizotypal, subclinically depressed, and control individuals.

BACKGROUND: Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. METHODS: Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. RESULTS: Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. CONCLUSIONS: The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.

Metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease from clinical to pathological characteristics: a multi-center cross-sectional study in real world.

BACKGROUND: The evaluation of patients with fatty liver as defined by metabolic dysfunction-associated fatty liver disease (MAFLD) in the real world remains poorly researched. This study aimed to analyse the clinical and histological features of patients with MAFLD and nonalcoholic fatty liver disease (NAFLD) and to characterize each metabolic subgroup of MAFLD. METHODS: A total of 2563 patients with fatty liver confirmed by ultrasonography and/or magnetic resonance tomography and/or liver biopsy-proven from three hospitals in China were included in the study. Patients were divided into different groups according to diagnostic criteria for MAFLD and NAFLD, and MAFLD into different subgroups. RESULTS: There were 2337 (91.2%) patients fitting the MAFLD criteria, and 2095 (81.7%) fitting the NAFLD criteria. Compared to patients with NAFLD, those with MAFLD were more likely to be male, had more metabolic traits, higher liver enzyme levels, and noninvasive fibrosis scores. Among the patients with liver biopsy, the extent of advanced fibrosis in cases with MAFLD was significantly higher than those with NAFLD, 31.8% versus 5.2% (P < .001); there was no significant difference in advanced fibrosis between obese cases and lean individuals in MAFLD (P > .05); MAFLD complicated with diabetes had significantly higher advanced fibrosis than those without diabetes (43.3% and 17.2%, respectively; P < .001). CONCLUSIONS: Patients with MAFLD have a higher degree of liver fibrosis than NAFLD patients. In addition, diabetic patients should be screened for fatty liver and liver fibrosis degree.

TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI. METHODS: The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot. RESULTS: Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group. CONCLUSION: TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Dental and skeletal maturation of Chinese male children with unilateral cleft lip and palate.

The aim of this study was to determine whether the relationship between dental age (DA), cervical stage (CS) and chronological age (CA) in Chinese male children with unilateral cleft lip and palate (UCLP) is similar to that of children without clefts. Panoramic and cephalometric radiographs of 105 male UCLP patients, aged from 8 to 16 years, were collected and compared to 210 age-matched healthy control males. The Demirjian and cervical vertebral maturation (CVM) methods were used to visually examine the radiographs and Spearman's correlation analysis was used to identify differences between the two groups with regards to CS, DA and CA. There was a significant positive correlation between DA and CA in both groups and the mean CA-DA difference was significantly higher in children with UCLP when compared to controls (0.319 vs. 0.003, p < 0.05). A significant delay in tooth development was detected in UCLP children from 10 to 12 years-of-age. Both the UCLP and control groups showed high correlations between CS and DA. Calcification stage D appeared only before CS3; however, from CS5 to 6, all teeth have almost completed their maturation phase. Chinese male UCLP patients are likely to experience delayed tooth development compared to healthy controls, especially during the fast-growing period. Evaluating the stages of tooth mineralization could represent a rapid method to assess growth potential.

[Network Meta-analysis of traditional Chinese medicine injections in treatment of chronic pulmonary heart disease].

Based on the network Meta-analysis, the efficacy and safety of different traditional Chinese medicine(TCM) injections in the treatment of chronic pulmonary heart disease(CPHD) were systematically evaluated. CNKI, Wanfang, VIP, SinoMed, Web of Science, PubMed, EMbase, and Cochrane Library were searched to collect randomized controlled trial(RCT) of TCM injection in the treatment of CPHD from inception to October 1, 2023. The quality of the included studies was evaluated by the bias risk assessment tool recommended by the Cochrane systematic evaluation manual version 5.3. Stata 17.0 and RevMan 5.4 software were used for statistical analysis of the data. Finally, 103 RCTs were included, involving 9 332 patients and 13 kinds of TCM injections. Network Meta-analysis yielded the following results.(1)In terms of improving the total clinical effective rate, the top three intervention measures in SUCRA ranking are Shuxuetong Injection + conventional western medicine>Ligustrazine Injection + conventional western medicine>Xinmailong Injection + conventional western medicine.(2)In terms of reducing pulmonary artery pressure, the top three intervention measures in SUCRA ranking are Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine>Ligustrazine Injection + conventional western medicine>Shenmai Injection + conventional western medicine.(3)In terms of improving left ventricular ejection fraction(LVEF), the top three intervention measures in SUCRA ranking are Xinmailong Injection + conventional western medicine>Danhong Injection + conventional western medicine>Ginkgo Damo Injection + conventional western medicine.(4) In terms of reducing brain natriuretic peptide(BNP), the top three intervention measures in SUCRA ranking are Xinmailong Injection + conventional wes-tern medicine>Ginkgo Damo Injection + conventional western medicine>Danhong Injection + conventional western medicine.(5) In terms of increasing arterial oxygen partial pressure(PaO_2) and reducing arterial carbon dioxide partial pressure(PaCO_2), the top three intervention measures in SUCRA ranking are Shenxiong Glucose Injection + conventional western medicine>Shenmai Injection + conventional western medicine>Shenfu Injection + conventional western medicine.(6) In terms of improving arterial oxygen saturation(SaO_2), the top three intervention measures in SUCRA ranking are Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine>Xinmailong Injection + conventional western medicine>Shenmai Injection + conventional western medicine.(7) In terms of increasing the percentage of forced expiratory volume in the first second(FEV_1%), the top three intervention measures in SUCRA ranking are Shenfu Injection + conventional western medicine>Tanshinone Sodium Ⅱ_A Sulfonate Injection + conventional western medicine>Shenmai Injection + conventional western medicine.(8) In terms of increasing the proportion of forced expiratory volume to forced vital capacity in the first second(FEV_1/FVC), the top three intervention measures in SUCRA ranking are Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine>Shuxuetong Injection + conventional western medicine>Danhong Injection + conventional western medicine.(9) In terms of safety, neither the experimental group nor the control group experienced any serious adverse drug reactions during the treatment period. In summary, combining TCM injection with conventional western medicine treatment can improve the comprehensive efficacy of treating CPHD, reduce pulmonary artery pressure, and improve cardiopulmonary function and arterial blood gas levels. However, due to the limitations of the quality and quantity of research methodology included, the above conclusions need to be further validated by more well-designed and high-quality RCT.

Carbon black as a colorimetric label for an immunochromatographic test strip for severe fever with thrombocytopenia syndrome virus detection.

To combat the ongoing threat posed by severe fever with thrombocytopenia syndrome virus (SFTSV), especially in underserved areas, there is an urgent need for an affordable and reliable point-of-care diagnostic tool. This study presents a carbon black-based immunochromatographic test strip (CB-ICTS) for the detection of SFTSV, which is both quick and easy to operate. The study optimized the specific steps for carbon black-labeled antibodies, as well as the amount of carbon black and anti-SFTSV antibody used. Under optimal experimental conditions, the linear range and limit of detection of the CB-ICTS were evaluated using different concentrations of SFTSV standard samples. The detection range of the CB-ICTS for SFTSV was found to be 0.1-1000 ng mL-1, with a limit of detection of 100 pg mL-1. The precision and accuracy of the CB-ICTS were assessed by examining spiked healthy human serum samples, which displayed recoveries ranging from 91.58 to 105.4% with a coefficient of variation of less than 11%. This work evaluated the specificity of the CB-ICTS using various biomarkers (CA125, AFP, CA199, CEA, and HCG) and demonstrated that the CB-ICTS is highly specific for detecting SFTSV, suggesting its potential for the early diagnosis of SFTSV. In addition, the study evaluated the CB-ICTS in serum samples from patients with SFTSV, and the results were highly consistent with those detected by the polymerase chain reaction (PCR) method. Overall, this study demonstrates the feasibility and effectiveness of using the CB-ICTS as a reliable point-of-care diagnostic tool for the early detection of SFTSV.

Transcriptome analysis of liver, gill and intestine in rainbow trout (Oncorhynchus mykiss) symptomatically or asymptomatically infected with Vibrio anguillarum.

Rainbow trout (Oncorhynchus mykiss), an important economic cold-water fish worldwide, is severely threatened by viruses and bacteria in the farming industry. The vibriosis outbreak has caused a significant setback to aquaculture. Vibrio anguillarum, one of the common disease-causing vibriosis associated with severe lethal vibriosis in aquaculture, infects fish mainly by adsorption and invasion of the skin, gills, lateral line and intestine. To investigate the defense mechanism of rainbow trout against the pathogen after infection with Vibrio anguillarum, trout were intraperitoneally injected by Vibrio anguillarum and divided into symptomatic group (SG) and asymptomatic group (AG) according to the phenotype. RNA-Seq technology was used to evaluate the transcriptional signatures of liver, gill and intestine of trout injected with Vibrio anguillarum (SG and AG) and corresponding control groups (CG(A) and CG(B)). The GO and KEGG enrichment analyses were used to investigate the mechanisms underlying the differences in susceptibility to Vibrio anguillarum. Results showed that in SG, immunomodulatory genes in the cytokine network were activated and tissue function-related genes were down-regulated, while apoptosis mechanisms were activated. However, AG responded to Vibrio anguillarum infection by activating complement related immune defenses, while metabolism and function related genes were up-regulated. Conclusively, a rapid and effective immune and inflammatory response can successfully defend Vibrio anguillarum infection. However, a sustained inflammatory response can lead to tissue and organ damage and cause death. Our results may provide a theoretical basis for breeding rainbow trout for disease resistance.

π-hole bonding: A new retention mechanism for the solid phase extraction of polycyclic aromatic hydrocarbons from the hexane extracts of soil samples.

In this work, the perfluorobenzene-bonded silica sorbent was tested to adsorb polycyclic aromatic hydrocarbons in hexane. In the comparison experiments, the perfluorobenzene-bonded sorbent's performance was better than octadecyl silica sorbent and phenyl-bonded silica sorbents, which indicated that the π-hole···π bonds between perfluorobenzene and the polycyclic aromatic hydrocarbons were stronger than π···π interactions and hydrophobic interactions in hexane. Then the perfluorobenzene-bonded silica sorbent was applied to solid-phase extraction of 15 polycyclic aromatic hydrocarbons from the hexane extracts of soil samples directly without the solvent replacement, which simplified the soil pretreatment process. And the results showed that under the optimal conditions, the proposed method for the determination of polycyclic aromatic hydrocarbons in the environment soil presented good recoveries and stabilities for the 10 heavier polycyclic aromatic hydrocarbons with the recoveries ranging from 75.1% to 104.6% and the relative standard deviations being in the range of 1.4%-5.8%. The limits of detection of the method varied from 0.1 to 2 ng/g. This work reveals the great application potential of the π-hole bond as a new retention mechanism in the field of solid-phase extraction.

Acacetin Alleviates Cardiac Fibrosis via TGF-ß1/Smad and AKT/mTOR Signal Pathways in Spontaneous Hypertensive Rats.

INTRODUCTION: Attenuating cardiac fibroblasts activation contributes to reducing excessive extracellular matrix deposition and cardiac structural remodeling in hypertensive hearts. Acacetin plays a protective role in doxorubicin-induced cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to investigate the potential molecular mechanisms underlying the protective role of acacetin on hypertension-induced cardiac fibrosis. METHODS: Echocardiography, histopathological methods, and Western blotting techniques were used to evaluate the anti-fibrosis effects in spontaneous hypertensive rat (SHR) which were daily intragastrically administrated with acacetin (10 mg/kg and 20 mg/kg) for 6 weeks. Angiotensin II (Ang II) was used to induce cellular fibrosis in human cardiac fibroblasts (HCFs) in the absence and presence of acacetin treatment for 48 h. RESULTS: Acacetin significantly alleviated hypertension-induced increase in left ventricular (LV) posterior wall thickness and LV mass index in SHR. The expressions of collagen-1, collagen-III, and alpha-smooth muscle actin (α-SMA) were remarkedly decreased after treatment with acacetin (n = 6, p < 0.05). In cultured HCFs, acacetin significantly attenuated Ang II-induced migration and proliferation (n = 6, p < 0.05). Moreover, acacetin substantially inhibited Ang II-induced upregulation of collagen-1 and collagen-III (n = 6, p < 0.05) and downregulated the expression of alpha-SMA in HCFs. Additionally, acacetin decreased the expression of TGF-ß1, p-Smad3/Smad3, and p-AKT and p-mTOR but increased the expression of Smad7 (n = 6, p < 0.05). Further studies found that acacetin inhibited TGF-ß1 agonist SRI and AKT agonist SC79 caused fibrotic effect. CONCLUSION: Acacetin inhibits the hypertension-associated cardiac fibrotic processes through regulating TGF-ß/Smad3, AKT/mTOR signal transduction pathways.

Associations between intraindividual reaction time variability and prospective memory performance in patients with schizophrenia and healthy controls.

Introduction: Patients with schizophrenia exhibit prospective memory (PM) impairment. Intraindividual reaction time variability (IIRTV) is an index of attentional control that is required for PM. This study examined the differences in IIRTV between patients with schizophrenia and healthy controls and the relationship between IIRTV and PM performance.Method: Thirty-nine patients with schizophrenia and forty-two healthy controls were recruited to complete a PM task and the Sustained Attention to Response Task. IIRTV was calculated as the coefficient of variation (mean/SD) of reaction time over correctly responded trials in these tasks.Results: Patients with schizophrenia showed lower PM accuracy and increased IIRTV, while the associations between PM accuracy and IIRTV were significant in healthy controls but not in patients with schizophrenia.Conclusion: These findings suggest impaired PM and relationship between PM and attentional control in patients with schizophrenia.

Comparative study on the clinical efficacy of small plate assisted anatomic plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of small plate assisted anatomical plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture. METHODS AND MATERIALS: The data of 68 patients with pilon fracture admitted to Hospital from June 2017 to June 2020 were retrospectively analyzed. Study group and control group were divided according to different operation methods, with 34 cases in each group. There were 28 cases of Rüedi and Allgöwer II type and 40 cases of Rüedi and Allgöwer III type. Perioperative period data, Ankle joint function score, visual analog scale (VAS) scores and the incidence of incision complications were analyzed between these two groups. RESULTS: There were no significant differences in full load time, fracture healing time between these two groups (P > 0.05). The operation time, intraoperative blood loss, length of hospital stay, Ankle joint function score and postoperative incision complication rate in observation group were lower than those in control group (P < 0.05). CONCLUSION: Small plate assisted anatomic plate is comparable to traditional double plate in the treatment of pilon fracture in terms of complete loading time, fracture healing time, but the former can shorten the operation time, reduce intraoperative blood loss and effectively reduce the incidence of postoperative complications.

Intramedullary nail fixation assisted by locking plate for complex subtrochanteric femur fractures: A retrospective study.

BACKGROUND: This study aims to compare therapeutic effects of two methods in complicated subtrochanteric femur fractures surgery: intramedullary nail fixation assisted with lateral monocortical locking plate versus intramedullary nail fixation assisted with supplementary cables. METHODS: From June 2015 to June 2020, seventy-seven patients with complex subtrochanteric fractures (i.e., Seinsheimer's classification type IV or V) were included in this study. Thirty-six patients (plate group) were operated using the intramedullary nail fixation assisted by lateral monocortical locking plate, and forty-one patients (cable group) were using the intramedullary nail fixation assisted by cables. The clinical information and demographic results were collected and compared. RESULTS: Operation time of plate group was shorter than cable group and the Incisions length of plate group was longer. The fluoroscopy times were 22.8 ± 8.2 in plate group and 33.0 ± 9.0 in cable group (p < 0.01). Compared with the cable group, patients in plate group used less cerclage cables (p < 0.01). Patients in the plate group has less medial cortex displacement compared with the cable group. (p = 0.038). As for the angular difference of neck shaft angle between operated hip and uninjured hip, plate group has less difference compared with the cable group. Time to union was 14.2 ± 3.1 weeks in plate group which is shorter than the cable group (17.9 ± 4.8 weeks). In terms of follow up period, number of malunion, Harris hip score, walking ability and traumatic hip rating scale, no significant differences were detected. CONCLUSIONS: Our results suggest that using lateral monocortical plate as an auxiliary way may have a longer surgical incision and more intraoperative blood loss, however, the operation time is shorter, the fluoroscopy times is less, and the time to union is shorter. Intramedullary nail fixation assisted by lateral monocortical locking plate may be a new option for patients with complex subtrochanteric femur fractures.

Effect of prehospital intubation on mortality rates in patients with traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVE: It is unclear if prehospital intubation improves survival in patients with traumatic brain injury. We performed a systematic review and meta-analysis to assess the impact of prehospital intubation on mortality rates of traumatic brain injury. METHODS: PubMed, CENTRAL, Web of Science, and Embase databases were searched without any language restriction up to 20 June 2022 for all types of comparative studies reporting survival of traumatic brain injury patients based on prehospital intubation. RESULTS: In total, 18 studies with 41,185 patients were eligible for inclusion. Meta-analysis showed that traumatic brain injury patients receiving prehospital intubation had higher odds of mortality as compared to those not receiving prehospital intubation. Meta-analysis of adjusted data also indicated that prehospital intubation was associated with increased odds of mortality in traumatic brain injury patients. The results did not change on sensitivity analysis. Subgroup analysis based on study type, the severity of traumatic brain injury, inclusion of isolated traumatic brain injury, emergency department intubation in the control group, and prehospital intubation group sample size demonstrated variable results. CONCLUSION: Heterogeneous data from mostly observational studies demonstrates higher mortality rates among traumatic brain injury patients receiving prehospital intubation. The efficacy of prehospital intubation is difficult to judge without taking into account multiple confounding factors.

[Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy].

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

Decreased Methylenetetrahydrofolate Reductase Activity Leads to Increased Sensitivity to para-Aminosalicylic Acid in Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most fatal diseases in the world. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the production of 5-methyltetrahydrofolate (5-CH3-THF), which is required for the de novo biosynthesis of methionine in bacteria. Here, we identified Rv2172c as an MTHFR in M. tuberculosis through in vitro and in vivo analyses and determined that the protein is essential for the in vitro growth of the bacterium. Subsequently, we constructed rv2172c R159N and L214A mutants in M. tuberculosis and found that these mutants were more sensitive to the antifolates para-aminosalicylic acid (PAS) and sulfamethoxazole (SMX). Combining biochemical and genetic methods, we found that rv2172c R159N or L214A mutation impaired methionine production, leading to increased susceptibility of M. tuberculosis to PAS, which was largely restored by adding exogenous methionine. Moreover, overexpression of rv2172c in M. tuberculosis could increase methionine production and lead to PAS resistance. This research is the first to identify an MTHFR in M. tuberculosis and reveals that the activity of this enzyme is associated with susceptibility to antifolates. These findings have particular value for antitubercular drug design for the treatment of drug-resistant TB.