A low-kiloelectronvolt focused ion beam strategy for processing low-thermal-conductance materials with nanoampere currents.

Ion beam-induced heat damage in thermally low conductive specimens such as biological samples is gaining increased interest within the scientific community. This is partly due to the increased use of FIB-SEMs in biology as well as the development of complex materials, such as polymers, which need to be analyzed. The work presented here looks at the physics behind the ion beam-sample interactions and the effect of the incident ion energy (set by the acceleration voltage) on inducing increases in sample temperature and potential heat damage in thermally low conductive materials such as polymers and biological samples. The ion beam-induced heat for different ion beam currents at low acceleration voltages is calculated using Fourier's law of heat transfer, finite element simulations, and numerical modelling results and compared to experiments. The results indicate that with lower accelerator voltages, higher ion beam currents in the nanoampere range can be used to pattern or image soft material and non-resin-embedded biological samples with increased milling speed but reduced heat damage.

Mortality associated with osteoporosis and pathological fractures in the United States (1999-2020): a multiple-cause-of-death study.

BACKGROUND: Osteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach. METHODS: Annual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test. RESULTS: From 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8-6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P < 0.05). White individuals had the highest number of deaths. The leading causes of death were heart diseases, chronic lower respiratory diseases, and alzheimer's disease. In addition, the number of deaths of patients with prostate cancer and breast cancer showed a significant downward trend, and the change of trend ratio between the two groups in different years was statistically significant (P < 0.05). CONCLUSIONS: Although mortality from osteoporosis with pathological fractures is decreasing, anti-osteoporosis therapy remains essential for elderly patients. Healthcare providers should remain vigilant for potential complications, including malignant neoplasms, and ensure timely diagnosis and treatment to further reduce mortality in this population.

NIR-II triggered Cu(I) phosphide for chemodynamic and photothermal periodontitis treatment: Efficient reduction of bacterial co-aggregation.

The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H2O2 levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu3P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting •OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate-a metabolite in periodontal biofilm-into H2O2, further amplifying CDT's potential. In vitro Cu3P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu3P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue in vivo periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified via the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care. STATEMENT OF SIGNIFICANCE: The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H2O2 level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu3P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu3P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management.

Potential of resveratrol in the treatment of systemic lupus erythematosus (Review).

Systemic lupus erythematosus (SLE) is a multi­system chronic autoimmune disease with a complex occurrence and development process, associated with immune disorders, uncertain prognosis, and treatment modalities which vary by patient and disease activity. At present, the clinical treatment of SLE mainly focuses on hormones and immunosuppressants. In recent years, the research on new treatment strategies for SLE has been booming, and strong preclinical results and clinical research have promoted the development of numerous drugs (such as rituximab and orencia), but numerous of these drugs have failed to achieve effectiveness in clinical trials, and there are some adverse reactions. Recent evidence suggests that resveratrol (RSV) has the effect of ameliorating immune disorders by inhibiting overactivation of immune cells. In the present review, advances in research on the protective effects and potential mechanisms of RSV against SLE are summarized and the potential potency of RSV and its use as a promising therapeutic option for the treatment of SLE are highlighted.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Preliminary nomogram model for predicting irreversible organ damage of patients with systemic sclerosis.

OBJECTIVE: To investigate predictive factors for irreversible organ damage in systemic sclerosis (SSc) and establish a nomogram model. METHODS: This retrospective study included patients with SSc who were treated at our hospital between March 2013 and March 2023. Irreversible organ damage included heart failure, respiratory failure, renal failure, and gangrene of the hands and feet. Cox and LASSO regression analyses were performed to determine the predictive factors. Based on the results, a nomogram model was developed. The model was evaluated using the C-indices, calibration plots, and DCA. RESULTS: A total of 361 patients with systemic sclerosis were randomly divided into the development (n = 181) and validation (n = 180) groups. Multivariate Cox regression analysis showed that age ≥65 years, weight loss, digital ulcers, mRSS ≥16, elevated creatinine, elevated myoglobin, elevated C-reactive protein, renal involvement, and cardiac involvement were independent risk factors. Based on the LASSO analysis, a nomogram model of irreversible organ damage was established. The C-indices of the development group at 24, 60, and 96 m were 96.7, 84.5, and 85.7, whereas those of the validation group at 24, 60, and 96 m were 86.6, 79.1, and 78.5, respectively. The results of the DCA showed that the nomogram can be used as a valuable tool to predict irreversible organ damage in patients with SSc. CONCLUSION: We included commonly used clinical indicators. According to the nomogram, the probability of irreversible organ damage can be calculated and high-risk patients can be identified.

Clinical characteristics of systemic sclerosis patients with occupational silicosis.

To explore the clinical characteristics of systemic sclerosis complicated with silicosis. The systemic sclerosis patients treated in the Guangxi Workers' Hospital and the People's Hospital of Guangxi Zhuang Autonomous Region from January 2000 to December 2020 were divided into the systemic sclerosis with silicosis group and the systemic sclerosis without silicosis group. Survival analysis was performed using Kaplan-Meier estimates the Cox proportional hazards model. A propensity score matching was applied in order to avoid the selection bias.Over the past 20 years, 72 systemic sclerosis patients with silicosis and 238 systemic sclerosis patients without silicosis were treated in the two hospitals. The systemic sclerosis patients with silicosis group had more males (P < 0.000),lower mean age at onset of SSc (P < 0.000), more frequent occurrence of weight loss (P = 0.028), smoking (P < 0.000), tuberculosis (P < 0.000), cardiac involvement (P < 0.000), ILD (P = 0.017), pulmonary hypertension (P = 0.024), elevated BNP (P < 0.000). With regards to the multivariate Cox regression analysis, silicosis was related with a higher overall mortality before (HR = 3.666, 95% CI = 1.440-11.234, p = 0.025) and after the propensity score matching analysis (HR = 2.817, 95% CI = 1.196-10.764, p = 0.014). Independent risk factors for overall mortality were Gangrene (HR = 3.003, 95% CI = 1.343-9.431), Cardiac involved (HR = 5.370, 95% CI = 1.910-15.472), Scl-70 (HR = 3.569, 95% CI = 1.333-10.869), Elevated BNP (HR = 2.135, 95% CI = 1.293-9.564).Concomitant silicosis worsens systemic sclerosis patients' prognoses. Gangrene, Scl-70, elevated BNP and cardiac involvement are independent risk factors for overall mortality. Key Points •Concomitant silicosis worsens SSc patients' prognoses. •For individuals with occupational exposure, close observation of the symptoms of SSc, early diagnosis, and interruption of exposure may improve the prognosis. •Gangrene, Scl-70, elevated BNP and cardiac involvement are independent risk factors for overall mortality.

Impact of Sjögren's syndrome on maternal and fetal outcomes following pregnancy: a systematic review and meta-analysis of studies published between years 2007-2022.

OBJECTIVE: To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy. METHODS: We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9. RESULTS: Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively). CONCLUSION: This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy.

Mortality associated with Sjögren's syndrome in the United States in the 1999-2020 period: A multiple cause-of-death study.

The study aimed to analyze the mortality and leading causes of death associated with Sjögren's syndrome (SS) in the United States (US) between 1999 and 2020 using a multicause approach. We analyzed mortality based on SS as the cause-of-death. Using mortality rates, number of deaths, and historical trends, we examined sex, age of death, comparisons of SS- and polymyalgia rheumatica-related deaths (multiple cause-of-death) in the last 20 years, changes in the ranking of causes of death when SS was the underlying cause-of-death (UCD) in the first and last 5 years of the last 20 years, and the number of deaths and standardized mortality (per 100,000 people) when SS combined with interstitial lung disease (ILD) or tumor was the multiple cause-of-death. An SS-standardized mortality trend chart and a trend line were created. In 22 years, the total number of SS-related deaths in the US was 7,817, including 7,016 women. When SS was the UCD and non-UCD, the standardized ratios of female-to-male deaths (per 100,000 people) were approximately 4.6-13:1 and 6.8-19.6:1, respectively. SS-related deaths were more common in people aged >60 years and concentrated in patients aged 60-79. In cases where SS and polymyalgia rheumatica were the multiple cause-of-death, the number of deaths and age-standardized mortality of SS and polymyalgia rheumatica increased, although lower in SS than in polymyalgia rheumatica. Regarding SS as the UCD, heart disease ranks first. Concerning the number of deaths and standardized mortality in the first (1999-2003) and second (2016-2020) 5 years, when SS-ILD and SS combined with tumors were the multiple causes of death, the number increased in the second 5 years compared to that in the first 5 years. When SS combined with COVID-19 was the multiple cause-of-death, 73 deaths occurred, comprising 64 females and 9 males. Death predominance was observed among women and patients aged 60-79 years with SS. Although the SS-standardized mortality rate was low, an increasing trend was observed. When SS was the primary cause-of-death, heart disease remained primarily involved, followed by malignant neoplasms. The number of patients with SS-ILD and SS combined with tumors in the past 22 years and the standardized mortality rate after 5 years increased compared with those of the previous 5 years. Concurrent SS and COVID-19 may be related to the increased SS deaths.

Sexual health in women with Sjogren's syndrome: A review.

BACKGROUND: Rheumatic diseases, mainly affecting women, including rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, etc., are chronic, inflammatory, autoimmune disorders that may involve multiple organs or systems and are closely related to sexual health, which is an important aspect of human physical and mental health. Sjogren's syndrome (SS) is the second most common rheumatic illnesses after rheumatoid arthritis with a female predominance. At present, the research on sexual health of female SS patients is still scarce and difficult to summarize. OBJECTIVES: The objective of our study was to systematically review the literature for the influence of maternal SS on sexual health, such as sexual function, sex hormones, fertility, and pregnancy outcomes. METHODS: We performed a comprehensive literature search based on PubMed and Web of science databases from inception to 1 November 2022. Outcomes were divided into 4 categories: sex hormones, sexual function, fertility, and pregnancy and offspring outcomes. RESULTS: A total of 756 potentially eligible papers were retrieved. After eliminating duplicate articles and reviewing the titles and abstracts to exclude records, we read the remaining 92 articles in full for further evaluation, and selected 42 studies. Results on sex hormones, sexual function, fertility and pregnancy and offspring outcomes were reported in 13, 12, 3 and 14 SS-related articles, respectively. The levels of some sex hormones in SS patients may have undergone changes. Female patients with SS have a high prevalence of sexual dysfunction compared with controls. Most studies suggested SS had an adverse impact on maternal and fetal outcomes following pregnancy. However, there is insufficient evidence that directly indicating the fertility of SS women is diminished. CONCLUSIONS: In summary, certain aspects of sexual health (sexual function, sex hormones and pregnancy outcomes) are impaired in SS women. Screening for sexual health problems in SS female should become an integral part of medical clinical practice. Rheumatologists should be aware of this association and collaborate with gynecologists, obstetricians, psychologists, and other experts on this issue to determine appropriate therapeutic approaches.