Ingenious Synergy of a Pathology-Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis.

Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M-M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M-M@I nanoparticles are taken up well by lipopolysaccharide-induced RAW 264.7 macrophages or bone marrow-derived macrophages (BMDMs). In vitro, the M-M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast-related enzymes. They also reduce the polarization of macrophages to a pro-inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen-induced arthritis, the M-M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology-specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae.

OBJECTIVES: To investigate the prevalence and mechanisms of ceftazidime/avibactam heteroresistance in KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, as well as the role of heteroresistance in the transition of ceftazidime/avibactam susceptibility to resistance. METHODS: Clinical KPC-KP isolates were obtained from a tertiary hospital in China from 2016 to 2017 and 2019 to 2020. Antimicrobial susceptibility was determined by the broth microdilution method. Population analysis profiles were used to assess ceftazidime/avibactam heteroresistance. WGS and molecular cloning were conducted to reveal heteroresistance mechanisms and molecular characteristics. RESULTS: The findings indicated that the transition of ceftazidime/avibactam susceptibility to resistance during the treatment of KPC-KP infection is primarily attributed to the heteroresistance exhibited by KPC-KP isolates towards ceftazidime/avibactam. Among 355 ceftazidime/avibactam-susceptible KPC-KP isolates (indicating a resistance rate of 0%), 41 (11.55%) exhibited ceftazidime/avibactam heteroresistance, with the primary mechanism being the presence of KPC mutant subpopulations. These KPC variants, arising from point mutations, deletions and insertions, significantly increased ceftazidime/avibactam resistance while alongside enhanced carbapenem susceptibility. Notably, 11 new KPC variants were identified. Furthermore, four heteroresistant isolates were caused by mixed infection involving subpopulations carrying NDM-1 or NDM-5. Phylogenetic analysis indicated that the clonal spread of ST11-KL64 KPC-KP may be correlated with the prevalence of heteroresistance. CONCLUSIONS: Ceftazidime/avibactam heteroresistance, primarily driven by pre-existing KPC variants, underscores the importance of considering heteroresistance in ceftazidime/avibactam therapeutics. Awareness of these dynamics is crucial for the effective and sustainable clinical application of ceftazidime/avibactam.

Fatty acid binding protein 5 inhibition attenuates pronociceptive cytokine/chemokine expression and suppresses osteoarthritis pain: A comparative human and rat study.

OBJECTIVE: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized. DESIGN: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA. Cytokine and chemokine release from human synovia incubated with a selective FABP5 inhibitor was profiled with cytokine arrays and ELISA. Immunohistochemical analyses were conducted for FABP5 in human and rat synovium. The efficacy of FABP5 inhibitors on pain was assessed in OA rats using incapacitance as an outcome. RNA-seq was then performed to characterize the transcriptomic landscape of synovial gene expression in OA rats treated with FABP5 inhibitor or vehicle. RESULTS: FABP5 was expressed in human synovium and FABP5 inhibition reduced the secretion of pronociceptive cytokines (interleukin-6 [IL6], IL8) and chemokines (CCL2, CXCL1). In rats, FABP5 was upregulated in the OA synovium and its inhibition alleviated incapacitance. The transcriptome of the rat OA synovium exhibited >6000 differentially expressed genes, including the upregulation of numerous pronociceptive cytokines and chemokines. FABP5 inhibition blunted the upregulation of the majority of these pronociceptive mediators. CONCLUSIONS: FABP5 is expressed in the OA synovium and its inhibition suppresses pronociceptive signaling and pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA.

High-performance Ag-TiO2 nanoparticle composite catalyst synthesized by pulsed laser ablation in liquid: properties, mechanism and preparation studies.

Precious metal doping can effectively improves the catalytic performance of TiO2. In this study, pulsed laser ablation in liquid (PLAL) is employed to integrate preparation with doping and control composite nanoparticle products by adjusting the laser action time to synthesise Ag-TiO2 composite nanoparticles with high catalytic performance. The generation and evolution of Ag-TiO2 nanoparticles are investigated by analysing particle size, microscopic morphology, crystalline phase, and other characteristics. The generation and doped-morphology evolution of composite nanoparticles are simulated based on thermodynamics, and the optimisation of Ag-doped structure on the composite nanomaterials is investigated based on density functional theory. The effect of Ag-TiO2 structural properties on its performance is examined under different catalytic conditions to determine optimal degradation conditions. In this study, the effect of laser ablation time on the doped structure during PLAL is analysed, which is of further research significance in exploring the structural evolution law of laser and composite nanoparticles, multi-variate catalytic performance testing, reduction of photogenerated carrier complexation rate, and expansion of its spectral absorption range, thereby providing the basis for practical production.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn's disease.

BACKGROUND: Adalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn's disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn's disease (CD), but implementation is challenging. AIM: To evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn's disease. METHODS: A prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn's disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the  ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients' quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. RESULTS: These investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment  in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05). CONCLUSION: Adalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn's disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

Correlation between thyroid hormone sensitivity and the risk of polycystic ovary syndrome.

OBJECTIVE: There has been some confusion in earlier research on the connection between thyroid function and polycystic ovary syndrome (PCOS). This research is aimed to probe into the correlation between thyroid condition and the risk of PCOS from a new standpoint of thyroid hormone sensitivity. METHODS: This research comprised 415 females with PCOS from Drum Tower Hospital Affiliated with the Medical School of Nanjing University, and 137 non-PCOS individuals were selected as the normal control. Based on free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH), we calculated the thyroid hormone sensitivity indices, which consist of Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI) and Free Triiodothyronine /Free thyroxine (FT3/FT4). The binary logistic regression model was adopted to investigate the correlation between thyroid hormone sensitivity indices with the risk of PCOS. Pearson or Spearman correlation analysis was employed to explore the association among thyroid-related measures with metabolic parameters in PCOS. RESULTS: Results of this research showed that females with PCOS had rising TFQI, TSHI, TT4RI, and FT3/FT4 levels compared with the control group. After adjustment for the impact of various covariates, there was no significant correlation between FT3/FT4 and the risk of PCOS; However, the odds ratio of the third and fourth vs. the first quartile of TFQI were 3.57(95% confidence interval [CI]:1.08,11.87) and 4.90(95% CI:1.38,17.38) respectively; The odds ratio of the fourth vs. the first quartile of TSHI was 5.35(95% CI:1.48,19.37); The odds ratio of the second vs. the first quartile of TT4RI was 0.27(95%CI 0.09,0.82). In addition, no significant correlation was observed between thyroid-related measures and metabolic measures in females with PCOS. CONCLUSIONS: A reduction in the sensitivity of central thyroid hormone is closely correlated with a higher risk of PCOS. Further research is necessary to corroborate our findings and the supporting mechanisms.

CYP1B1-AS1 Delays the Malignant Progression of Colorectal Cancer by Binding with NOP58.

BACKGROUND: Colorectal cancer (CRC) is a prevalent type of gastrointestinal cancer, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. CYP1B1-AS1, as non-coding RNA, plays an important role in tumorigenesis and progression. However, the mechanism by which CYP1B1-AS1 acts in CRC is not yet understood. AIMS: The objective of this study was to investigate how CYP1B1-AS1 contributes to the development of CRC, and provide a base for CRC diagnosis and treatment. METHODS: RT-qPCR was used to detect the expression level of CYP1B1-AS1 in CRC and adjacent tissues. CCK-8, Edu, scratch healing, and transwell experiments were used to detect the changes of proliferation, migration, and invasion ability of CRC cells after overexpression or knockdown of CYP1B1-AS1 respectively. The RNA binding protein NOP58 combined with CYP1B1-AS1 was verified by RIP and RNA Pull-down experiments. Functional recovery experiments validated the interaction between CYP1B1-AS1 and NOP58 in CRC cells. The changes of EMT-related proteins were detected by Western blot, and the half-life of transcription factor SNAIL mRNA were detected by RT-qPCR after overexpression or knockdown of NOP58. RESULTS: CYP1B1-AS1 was found to be significantly downregulated in CRC compared to adjacent noncancerous tissues. Experiments conducted in vitro and in vivo confirmed that upregulation of CYP1B1-AS1 significantly inhibited the proliferation, migration, and invasion of CRC cells. In addition, CYP1B1-AS1 can directly bind to NOP58 and negatively regulate NOP58. The effect of overexpression CYP1B1-AS1 was reversed by NOP58 overexpression. NOP58 regulates the EMT process of CRC cells by affecting the stability of EMT-related transcription factor SNAIL mRNA, and then affects the progress of CRC. CONCLUSION: This research proves that CYP1B1-AS1 can inhibit the occurrence of EMT in CRC by binding with NOP58, thus delaying the progress of CRC. This finding indicates that CYP1B1-AS1 may be a novel biomarker to improve the diagnosis and treatment of CRC.

A case of herpes zoster secondary to monkeypox in a young man.

A 19-year-old young man presented with prodromal symptoms including fever and sore throat, followed by the development of scattered rashes in the perianal and penile regions. Monkeypox (MPX) was confirmed using polymerase chain reaction (PCR) of lesions. On the third day after complete resolution of the initial rash, the patient developed a new rash, which was diagnosed as secondary herpes zoster (HZ). Therefore, clinicians should not only focus on the accurate diagnosis of monkeypox, but also be alert to secondary herpes zoster.

Impact of Tibetan ethnicity and residence altitude on complications during total knee arthroplasty and difficulties of measurement of perioperative blood loss.

PURPOSE: Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA. METHODS: We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500 m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression. RESULTS: Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects. CONCLUSIONS: Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients.

Ceftazidime-Decorated Gold Nanoparticles: a Promising Strategy against Clinical Ceftazidime-Avibactam-Resistant Enterobacteriaceae with Different Resistance Mechanisms.

Nanoparticle-based antibiotic delivery systems are essential in combating antibiotic-resistant bacterial infections arising from acquired resistance and/or biofilm formation. Here, we report that the ceftazidime-decorated gold nanoparticles (CAZ_Au NPs) can effectively kill clinical ceftazidime-avibactam-resistant Enterobacteriaceae with various resistance mechanisms. Further study of underlying antibacterial mechanisms suggests that CAZ_Au NPs can damage the bacterial cell membrane and increase the level of intracellular reactive oxygen species. Moreover, CAZ_Au NPs show great potential in inhibiting biofilm formation and eradicating mature biofilms via crystal violet and scanning electron microscope assays. In addition, CAZ_Au NPs demonstrate excellent performance in improving the survival rate in the mouse model of abdominal infection. In addition, CAZ_Au NPs show no significant toxicity at bactericidal concentrations in the cell viability assay. Thus, this strategy provides a simple way to drastically improve the potency of ceftazidime as an antibiotic and its use in further biomedical applications.

ATP-P2X7R-mediated microglia senescence aggravates retinal ganglion cell injury in chronic ocular hypertension.

BACKGROUND: Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2X7R in the mediation of microglia senescence and glaucoma progression. METHODS: Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry. RESULTS: ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2X7R was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2X7R was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2X7R induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage. CONCLUSION: ATP-P2X7R induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2X7R may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.

Acetylcysteine increases sensitivity of ceftazidime-avibactam-resistant enterobacterales with different enzymatic resistance to ceftazidime-avibactam in vitro and in vivo.

BACKGROUND: Ceftazidime-avibactam (CZA) improves treatment outcomes for infections caused by carbapenem-resistant organisms, but has led to serious bacterial resistance. Acetylcysteine (NAC) is an approved medication that protects the respiratory tract through antioxidant and anti-inflammatory effects. RESULTS: This study found that NAC combined with CZA effectively inhibits the growth of CZA-resistant clinical Enterobacterales strains. The CZA/NAC combination inhibits biofilm formation in vitro and decreases bacterial burden in a mouse thigh infection model. The combination is biocompatible and primarily increases cell membrane permeability to cause bacterial death. CONCLUSIONS: These findings prove that the CZA/NAC combination has potential as a treatment for CZA-resistant Enterobacterales infections.

Study of Combined Effect of Bacteriophage vB3530 and Chlorhexidine on the Inactivation of Pseudomonas aeruginosa.

BACKGROUND: Chlorhexidine (CHG) is a disinfectant commonly used in hospitals. However, it has been reported that the excessive use of CHG can cause resistance in bacteria to this agent and even to other clinical antibiotics. Therefore, new methods are needed to alleviate the development of CHG tolerance and reduce its dosage. This study aimed to explore the synergistic effects of CHG in combination with bacteriophage against CHG-tolerant Pseudomonas aeruginosa (P. aeruginosa) and provide ideas for optimizing disinfection strategies in clinical environments as well as for the efficient use of disinfectants. METHODS: The CHG-tolerant P. aeruginosa strains were isolated from the First Affiliated Hospital of Wenzhou Medical University in China. The bacteriophage vB3530 was isolated from the sewage inlet of the hospital, and its genome was sequenced. Time-killing curve was used to determine the antibacterial effects of vB3530 and chlorohexidine gluconate (CHG). The phage sensitivity to 16 CHG-tolerant P. aeruginosa strains and PAO1 strain was detected using plaque assay. The emergence rate of resistant bacterial strains was detected to determine the development of phage-resistant and CHG-tolerant strains. Finally, the disinfection effects of the disinfectant and phage combination on the surface of the medical devices were preliminarily evaluated. RESULTS: The results showed that (1) CHG combined with bacteriophage vB3530 significantly inhibited the growth of CHG-resistant P. aeruginosa and reduced the bacterial colony forming units (CFUs) after 24 h. (2) The combination of CHG and bacteriophage inhibited the emergence of phage-resistant and CHG-tolerant strains. (3) The combination of CHG and bacteriophage significantly reduced the bacterial load on the surface of medical devices. CONCLUSIONS: In this study, the combination of bacteriophage vB3530 and CHG presented a combined inactivation effect to CHG-tolerant P. aeruginosa and reduced the emergence of strains resistant to CHG and phage. This study demonstrated the potential of bacteriophage as adjuvants to traditional disinfectants. The use of bacteriophage in combination with commercial disinfectants might be a promising method for controlling the spread of bacteria in hospitals.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Ubiquitin-Like Protein FAT10 Promote Colorectal Cancer Progression by Affecting the Ubiquitination of Capn4.

BACKGROUND: Emerging evidence showed that FAT10 is a vital regulator of tumor occurrence and development. The molecular mechanisms underlying the specific role of FAT10 in colorectal cancer (CRC) are not yet known. AIMS: To investigate whether FAT10 participates in the proliferation, invasion and metastasis of CRC. METHODS: This study investigated the function and clinical significance of FAT10 protein expression in CRC. Furthermore, over-expression and knockdown experiments of FAT10 were developed to explore their effects on CRC cell migration and proliferation. Moreover, a molecular mechanism of FAT10 regulate calpain small subunit 1(Capn4) was explored. RESULTS: In this research, the FAT10 expression level was elevated in CRC tissues compared to corresponding normal tissues. In addition, the elevated FAT10 expression level is significantly linked to advanced clinical stage and poor CRC prognosis. Furthermore, a very high expression of FAT10 was observed in CRC cells, and FAT10 overexpression significantly enhanced the in vivo proliferation, invasion, and metastasis of the cells, whereas knockdown of FAT10 inhibited all these cellular factors in both in vivo and in vitro environments. Moreover, the outcomes of this study suggested that FAT10 enhances colorectal cancer progression through enhancement of Capn4 expression, leading to the progression of various human tumors, as reported by previous research. The mechanism via which FAT10 promotes CRC cells proliferation, invasion, and metastasis involves modification of the ubiquitination and degradation processes of Capn4. CONCLUSION: FAT10 is a vital regulator of the tumorigenesis and advancement of CRC, thus serving as a promising pharmaceutical target for treating CRC patients.

A potential strategy against clinical carbapenem-resistant Enterobacteriaceae: antimicrobial activity study of sweetener-decorated gold nanoparticles in vitro and in vivo.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) present substantial challenges to clinical intervention, necessitating the formulation of novel antimicrobial strategies to counteract them. Nanomaterials offer a distinctive avenue for eradicating bacteria by employing mechanisms divergent from traditional antibiotic resistance pathways and exhibiting reduced susceptibility to drug resistance development. Non-caloric artificial sweeteners, commonly utilized in the food sector, such as saccharin, sucralose, acesulfame, and aspartame, possess structures amenable to nanomaterial formation. In this investigation, we synthesized gold nanoparticles decorated with non-caloric artificial sweeteners and evaluated their antimicrobial efficacy against clinical CRE strains. RESULTS: Among these, gold nanoparticles decorated with aspartame (ASP_Au NPs) exhibited the most potent antimicrobial effect, displaying minimum inhibitory concentrations ranging from 4 to 16 µg/mL. As a result, ASP_Au NPs were chosen for further experimentation. Elucidation of the antimicrobial mechanism unveiled that ASP_Au NPs substantially elevated bacterial reactive oxygen species (ROS) levels, which dissipated upon ROS scavenger treatment, indicating ROS accumulation within bacteria as the fundamental antimicrobial modality. Furthermore, findings from membrane permeability assessments suggested that ASP_Au NPs may represent a secondary antimicrobial modality via enhancing inner membrane permeability. In addition, experiments involving crystal violet and confocal live/dead staining demonstrated effective suppression of bacterial biofilm formation by ASP_Au NPs. Moreover, ASP_Au NPs demonstrated notable efficacy in the treatment of Galleria mellonella bacterial infection and acute abdominal infection in mice, concurrently mitigating the organism's inflammatory response. Crucially, evaluation of in vivo safety and biocompatibility established that ASP_Au NPs exhibited negligible toxicity at bactericidal concentrations. CONCLUSIONS: Our results demonstrated that ASP_Au NPs exhibit promise as innovative antimicrobial agents against clinical CRE.

The Impact of Perioperative Use of Nonbiologic Disease-Modifying Anti-rheumatic Drugs on Perioperative Blood Loss and Complications in Patients Who Have Rheumatoid Arthritis Undergoing Total Knee Arthroplasty.

BACKGROUND: The use of disease-modifying antirheumatic drugs (DMARDs) before total knee arthroplasty (TKA) was associated with increased risk of postoperative periprosthetic joint and wound infections as well as worse platelet function in patients who have knee rheumatoid arthritis (RA). This study investigated the effects of DMARDS on perioperative blood loss, complications, and blood transfusion in patients undergoing TKA for knee RA. METHODS: We retrospectively enrolled patients undergoing TKA for knee RA at our hospital between 2017 and 2021 who received DMARDs (n = 73) or not (n = 84). Every RA patient was matched with patients who had osteoarthritis (OA) in a ratio of 1:1 or 1:2. Primary outcomes were intraoperative and perioperative blood losses, while secondary outcomes were complications and allogeneic transfusions. RESULTS: The mean total (804 versus 728 mL (mL), P = .114), mean intraoperative (113 versus 101 mL, P = .488), or hidden blood losses (705 versus 640 mL, P = .340) did not differ statistically between RA patients who received DMARDs versus those who did not. RA patients who received DMARDs showed significantly greater mean total (804 versus 654 mL, P = .001), intraoperative (113 versus 75 mL, P = .002), and hidden blood losses (705 versus 560 mL, P = .016) than OA patients. No statistical differences were found in complications or allogeneic transfusions. CONCLUSION: Although RA patients experienced greater perioperative blood loss than OA patients, there was no statistical difference in perioperative blood loss, complications, or allogeneic transfusions between RA patients who received DMARDs and those who did not.

Manufacture of TiO2 nanoparticles with high preparation efficiency and photocatalytic performance by controlling the parameters of pulsed laser ablation in liquid.

This study proposes a method to improve the production efficiency and photocatalytic performance of TiO2 nanoparticles using the pulsed laser ablation in liquid (PLAL) method to optimise preparation parameters. In this study, the variation of particle size, morphology, preparation, and catalytic efficiency due to the increase in the number of pulses is studied. The mechanism of particle morphology change is analysed using thermodynamic simulation. The density functional theory (DFT) is used to calculate and characterise the reason why the special structure formed by particle breaking improves the photocatalytic performance. In addition, the influence of the law of solution height on particle breakage is summarised to obtain an optimised preparation parameter. The proposed method provides a reference for the selection of parameters in actual production.

Microglia-derived TNF-α mediates Müller cell activation by activating the TNFR1-NF-κB pathway.

Microglia and its interaction with Müller cells are responsible to retinal surveillance during retinal neurodegeneration, however, the role and mechanism of microglia-derived tumor necrosis factor (TNF)-α in the activation of retinal Müller cells have not been fully elucidated. In the present study, primary microglia and Müller cells were isolated from newborn Sprague-Dawley (SD) rats with purities of 88.2 ± 6.2% and 92.2 ± 2.2%, respectively. By performing immunofluorescence and Western blot analysis, we found that TNF receptor (TNFR)-1 and TNFR2 were expressed in Müller cells. After co-cultured with microglia-conditioned medium (MCM), the elevated mRNA levels of glial fibrillary acidic protein (GFAP), proinflammatory factors (TNF-α, IL-1ß, CXCL-1, CSF-1, NOS2, COX2) and decreased CNTF mRNA levels were found in Müller cells. However, pretreatment with R-7050 (a TNF-α receptor inhibitor) or anti-TNFR1 significantly abrogated the changes. Simultaneously, pretreatment with anti-TNFR2 slightly inhibited the expression of GFAP in MCM-incubated Müller cells. Meanwhile, anti-TNFR1 treatment reversed the increased expression of CSF-1 and IL-1ß induced by TNF-α. Compared to the control groups, the phosphorylation of NF-κB P65, MAPK P38 and ERK1/2 in TNF-α-treated Müller cells was significantly increased. Nevertheless, pretreatment with anti-TNFR1 inhibited the phosphorylation of NF-κB P65 and MAPK p38, especially NF-κB P65. Additionally, pretreatment with Bay117082 (an NF-κB inhibitor) also significantly inhibited NF-κB P65 phosphorylation and GFAP expression. Moreover, anti-TNFR1 and Bay117082 treatment reduced NF-κB P65 phosphorylation of Müller cells induced by MCM. These results suggested that microglia-derived TNF-α served as a vital role in regulating Müller cells activation during retinal neurodegeneration.