The effects of cGAS-STING inhibition in liver disease, kidney disease, and cellular senescence.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is one of the fundamental mechanisms of the body's defense, which responds to the abnormal presence of double-stranded DNA in the cytoplasm to establish an effective natural immune response. In addition to detecting microbial infections, the cGAS pathway may be triggered by any cytoplasmic DNA, which is absent from the normal cytoplasm, and only conditions such as senescence and mitochondrial stress can lead to its leakage and cause sterile inflammation. A growing body of research has shown that the cGAS-STING pathway is strongly associated with sterile inflammation. In this study, we reviewed the regulatory mechanisms and biological functions of the cGAS-STING pathway through its involvement in aseptic inflammation in liver disease, kidney disease, and cellular senescence.

Age-related efficacy of immunotherapies in advanced non-small cell lung cancer: a comprehensive meta-analysis.

OBJECTIVE: The reported impact of age on the effectiveness of emerging immunotherapies in patients with advanced non-small cell lung cancer (NSCLC) has been inconsistent in clinical trials, largely due to an underrepresentation of older individuals. This meta-analysis aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) in older patients with NSCLC. MATERIALS AND METHODS: The literature up to April 2024 was reviewed to identify articles meeting the criteria for inclusion. Hazard ratios (HRs) for overall survival (OS) across various age groups were examined. The ratio of HR (RHR) was computed and combined for each study. RESULTS: A preliminary search identified 118 articles, with 13 being phase II or III randomized clinical trials comparing the efficacy of nivolumab, avelumab, ipilimumab, pembrolizumab, atezolizumab, and chemotherapy with or without antiangiogenic therapy. The analysis revealed that the HR for OS was 0.75 (95 % CI: 0.70-0.80, P=0.080) in patients aged under 75 years and 0.87 (95 % CI: 0.74-1.01, P=0.913) in patients aged 75 years and older. The combined RHR for patients aged 75 years and above versus those aged under 75 years was 1.14 (95 % CI: 0.97-1.34, P=0.697). There was no significant difference in OS benefit between patients over 75 years and younger patients (P=0.105). Subgroup analyses indicated that the benefit of OS was consistent across all subgroups and age groups. CONCLUSIONS: Our investigation found no significant differences in the efficacy of immunotherapy for patients with NSCLC aged 75 years and older compared to those under 75 years old. This suggests that the efficacy of immunotherapy against NSCLC is consistent across age groups.

Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys.

DNA methylation plays a crucial role in environmental adaptations. Here, using whole-genome bisulfite sequencing, we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey ( Rhinopithecus bieti) and the closely related golden snub-nosed monkey ( R. roxellana). Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys, suggesting a higher prevalence of hypermethylated genomic regions in the former. Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion, vesicular formation and trafficking, hemoglobin function, cell cycle regulation, and neuronal differentiation. These results suggest that the high-altitude-related epigenetic modifications are extensive, involving a complete adaptation process from the inhibition of single Ca 2+ channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation. Functional assays demonstrated that overexpression or down-regulation of candidate genes, such as SNX10, TIMELESS, and CACYBP, influenced cell viability under stress conditions. Overall, this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations, thereby deepening our understanding of the mechanisms underlying environmental adaptations.

Loss-of-function of LIGULELESS1 activates the jasmonate pathway and promotes maize resistance to corn leaf aphids.

Corn leaf aphids (Rhopalosiphum maidis) are highly destructive pests of maize (Zea mays) that threaten growth and seed yield, but resources for aphid resistance are scarce. Here, we identified an aphid-resistant maize mutant, resistance to aphids 1 (rta1), which is allelic to LIGULELESS1 (LG1). We confirmed LG1's role in aphid resistance using the independent allele lg1-2, allelism tests and LG1 overexpression lines. LG1 interacts with, and increases the stability of ZINC-FINGER PROTEIN EXPRESSED IN INFLORESCENCE MERISTEM (ZIM1), a central component of the jasmonic acid (JA) signalling pathway, by disturbing its interaction with the F-box protein CORONATINE INSENSITIVE 1a (COI1a). Natural variation in the LG1 promoter was associated with aphid resistance among inbred lines. Moreover, a loss-of-function mutant in the LG1-related gene SPL8 in the dicot Arabidopsis thaliana conferred aphid resistance. This study revealed the aphid resistance mechanism of lg1, providing a theoretical basis and germplasm for breeding aphid-resistant crops.

Clinical Predictors of Medication Compliance in Patients With Acute Herpetic Neuralgia.

PURPOSE: Pain is one of the most common and harmful symptoms experienced by individuals with acute herpetic neuralgia (AHN). In this population, studies to determine the causes that affect patients taking medications compliance are rare. This study aimed to construct a predictive model for medication compliance of patients with AHN and to verify its performance. DESIGN AND METHODS: In this prospective study of 398 patients with AHN who were discharged from a tertiary hospital with medications from July 2020 to October 2022, we used logistic regression analysis to explore the predictive factors of medication compliance of patients with AHN and to construct a nomogram. The area under the curve was used to evaluate the predictive effect of the model. RESULTS: A predictive model of drug compliance of patients with AHN was constructed based on the following four factors: disease duration, pain severity before treatment, medication beliefs, and comorbidity of chronic diseases. The area under the curve of the model was 0.766 (95% confidence interval [0.713, 0.819]), with a maximum Youden's index of 0.431, sensitivity of 0.776, and specificity of 0.655. A linear calibration curve was found with a slope close to 1. CONCLUSIONS: The prediction model constructed in this study had good predictive performance and provided a reference for early clinical screening of independent factors that affected the medication compliance of patients with AHN.

PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.

Secondary Polycythemia May Be an Early Clinical Manifestation of Multiple Myeloma: A Case Report.

Multiple myeloma (MM) is a malignancy of plasma cells that can cause anemia due to renal failure and bone marrow failure. Secondary polycythemia (SE) is a clinically rare disease that involves the overproduction of red blood cells. To our knowledge, the association of multiple myeloma and polycythemia has been reported, but the association of SE and multiple myeloma is rare and has been infrequently reported in literature. In contrast to anemia, the presence of polycythemia in multiple myeloma patients is a rare finding. A patient of IgA-λ multiple myeloma with secondary erythrocytosis recently admitted to our department is now reported as follows and relevant literature is reviewed to improve clinicians' awareness of such rare comorbidities.

Deep cervical lymph nodes in Parkinson's disease and atypical Parkinson's disease: A potential ultrasound biomarker for differential diagnosis.

Background: Parkinson's disease (PD) is a common degenerative disease caused by abnormal accumulation of α-synuclein. The glymphatic pathway is essential for removing macromolecular proteins including α-synuclein from the brain, which flows into deep cervical lymph nodes (DCLNs) through meningeal lymphatics. As a terminal station for the cerebral lymphatic system drainage, DCLNs can be easily assessed clinically. Objectives: Although the drainage function of the cerebral lymphatic system is impaired in PD, the correlation between DCLNs and PD remains unknown. Design: Single-center retrospective cross-sectional study. Methods: The size of the DCLNs were measured using ultrasound. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale and other scales were used to assess PD motor and non-motor symptoms. Results: Compared with the healthy control (HC) and the atypical Parkinson's disease (AP) groups, the size of the second and third DCLNs in the Parkinson's disease (PD) group was significantly smaller (P < .05). The width diameter of the third DCLN (DCLN3(y)) was significantly smaller in the PD group than in the AP group (P = .014). DCLN3(y) combined with a variety of clinical features improved the sensitivity of AP identification (sensitivity = .813). Conclusion: DCLNs were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved.

Deep cervical lymph nodes, a potential marker for the diagnosis of PD and AP. Deep cervical lymph nodes (DCLNs) were able to distinguish HC, PD and AP and were mainly located in Robbins ΙΙA level. PD and AP were associated with different factors that influenced the size of the DCLNs. DCLN3(y) plays an important role in differentiating PD from AP, which, combined with other clinical features, has the ability to distinguish PD from AP; in particular, the sensitivity of AP diagnosis was improved. DCLN has potential diagnostic value in differentiating PD from AP.

Oxaliplatin-associated shock in stage III colorectal cancer patients: real-world evidence in Taiwan.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012­2016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.

Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial.

BACKGROUND: Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs. METHODS: A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency. FINDINGS: The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC = 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting. CONCLUSIONS: This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy. FUNDING: Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).

Heat acclimation alleviates the heat stress-induced impairment of vascular endothelial cells.

Heat acclimation (HA) is found to help decrease the incidence of heat-related illnesses such as heat syncope and exertional heat stroke. However, the response of vascular endothelial cells to HA remain to be elucidated. In this study, mouse brain microvascular endothelial cells (bEnd.3), human umbilical vein endothelial cells (HUVEC), and human aortic endothelial cells (HAEC) were selected. The cells were first subjected to HA at 40 ℃ for 2 h per day for 3 days, and then subjected to heat stress at 43 ℃ for 2 h or 4 h. After heat stress, HA-pretreated cells showed a significant increase in cell viability, cell integrity, a decrease in the proportion of S phase cells, cell apoptosis, and cytoskeletal shrinkage compared with the cells without HA pretreatment. Additionally, the expression of VEGF, ICAM-1, iNOS and EPO in HA-pretreated cells significantly increased. We also presented evidence that HA upregulated HSP70 and bcl-2, while downregulated p-p53 and bax. Notably, the suppression of HSP70 expression attenuated the protective role of heat acclimation. Furthermore, HA mitigated injuries in vital organs of mice exposed to heat stress. Conclusively, these findings indicated the HA can increase the vitality of vascular endothelial cells after heat stress, partially restore the function of vascular endothelial cells, and this protective effect may be related to the upregulation of HSP70 expression.

Response Properties of Electrorheological Composite Hydrophilic Elastomers Based on Different Morphologies of Magnesium-Doped Strontium Titanate.

As smart materials, electrorheological elastomers (EREs) formed by pre-treating active electrorheological particles are attracting more and more attention. In this work, four Mg-doped strontium titanate (Mg-STO) particles with spherical, dendritic, flake-like, and pinecone-like morphologies were obtained via hydrothermal and low-temperature co-precipitation. XRD, SEM, Raman, and FT-IR were used to characterize these products. The results showed that Mg-STOs are about 1.5-2.0 µm in size, and their phase structures are dominated by cubic crystals. These Mg-STOs were dispersed in a hydrogel composite elastic medium. Then, Mg-STO/glycerol/gelatin electrorheological composite hydrophilic elastomers were obtained with or without an electric field. The electric field response properties of Mg-doped strontium titanate composite elastomers were investigated. We concluded that dendritic Mg-STO composite elastomers are high-performance EREs, and the maximum value of their energy storage was 8.70 MPa. The significant electrorheological performance of these products is helpful for their applications in vibration control, force transducers, smart structures, dampers, and other fields.

Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.

Mammalian cytosolic selenoprotein thioredoxin reductase (TXNRD1) is crucial for maintaining the reduced state of cellular thioredoxin 1 (TXN1) and is commonly up-regulated in cancer cells. TXNRD1 has been identified as an effective target in cancer chemotherapy. Discovering novel TXNRD1 inhibitors and elucidating the cellular effects of TXNRD1 inhibition are valuable for developing targeted therapies based on redox regulation strategies. In this study, we demonstrated that butein, a plant-derived small molecule flavonoid, is a novel TXNRD1 inhibitor. We found that butein irreversibly inhibited recombinant TXNRD1 activity in a time-dependent manner. Using TXNRD1 mutant variants and LC-MS, we identified that butein modifies the catalytic cysteine (Cys) residues of TXNRD1. In cellular contexts, butein promoted the accumulation of reactive oxygen species (ROS) and exhibited cytotoxic effects in HeLa cells. Notably, we found that pharmacological inhibition of TXNRD1 by butein overcame the cisplatin resistance of A549 cisplatin-resistant cells, accompanied by increased cellular ROS levels and enhanced expression of p53. Taken together, the results of this study demonstrate that butein is an effective small molecule inhibitor of TXNRD1, highlighting the therapeutic potential of inhibiting TXNRD1 in platinum-resistant cancer cells.

Effect Analysis of the HFMEA Model Applied in Sputum Specimen Management Among Patients with Tuberculosis.

Objective: Accurate diagnosis is very important to block the transmission of tuberculosis. The quality of sputum culture affects the diagnostic accuracy. The quality of sputum samples is not optimistic. Therefore, this study investigated whether health care failure mode and effect analysis (HFMEA) can improve specimen quality and detection efficiency in sputum specimen management in tuberculosis departments. Methods: This study is a non-randomized controlled trial study. A convenience sampling method was used to select 110 patients who visited the Department of Tuberculosis of the Second Hospital of Nanjing from September to November 2022 and December 2022 to February 2023 as the control group and the experimental group. Control groups followed standard operating procedures for sputum specimen collection. In the experimental group, HFMEA model was used to control the quality on this basis. After 3 months of intervention, the qualified rate and positive detection rate of sputum samples were compared between the two groups. Results: A total of 634 sputum specimens were included in the experimental group and 647 in the control group. Compared with the control group, the qualification rate of sputum specimens was higher in the experimental group (84.54% vs 79.13%); the positive detection rates of the X-Pert assay (27.88% vs 16.19%), sputum culture (20.29% vs 12.68%), and sputum smear (22.29% vs 15.81%) were all higher in the experimental group (all P < 0.05). Patients in the experimental group had higher knowledge mastery and nurse sputum sample management scores (P < 0.05). However, patient satisfaction with sputum specimen management in the experimental group was lower than in the control group (7.72 ± 0.74 vs 8.38 ± 0.85, P < 0.001). Conclusion: The application of the HFMEA model in sputum specimen management can effectively improve specimen quality and positive detection rates.

[Effect of umbilical moxibustion on intestinal flora in patients with subthreshold depression].

OBJECTIVE: To observe the clinical efficacy of umbilical moxibustion for subthreshold depression (SD) and its effect on intestinal flora, and to explore its mechanism. METHODS: Thirty-six SD patients were recruited as the SD group (1 case dropped out, 2 cases excluded), and 36 healthy subjects were recruited as the healthy control group (1 case excluded). The SD group was treated with umbilical moxibustion, once a week, a total of 8 times were required. The healthy control group did not receive any intervention. Hamilton depression scale 17-item (HAMD-17) and Center for Epidemiologic Studies depression scale (CES-D) scores were observed in the SD group before and after treatment, and the clinical efficacy was evaluated. Fecal samples were collected in the SD group before and after treatment and in the healthy control group when enrolled, the intestinal flora was analyzed by 16S rRNA sequencing technology. RESULTS: The HAMD-17 and CES-D scores after treatment in the SD group were reduced compared with those before treatment (P<0.05), and the total effective rate was 90.9% (30/33). Compared with the healthy control group, Sobs index, Shannon index and Ace index were reduced in the SD group before treatment (P<0.05), Simpson index was increased (P<0.05), the relative abundance of Escherichia-Shigella was increased (P<0.01), the relative abundance of Eubacterium_hallii_group, Ruminococcus, Christensenellaceae_R-7_ group, Paraprevotella was decreased (P<0.05, P<0.01). Compared before treatment, the relative abundance of Escherichia- Shigella after treatment in the SD group was decreased (P<0.01), the relative abundance of Ruminococcus, Christensenaceae_R-7_group, Paraprevotella was increased (P<0.01, P<0.05). Christensenellaceae_R-7_group and Paraprevotella were negatively correlated with the CES-D score (P<0.01, P<0.05). Escherichia-Shigella was positively correlated with the HAMD-17 score (P<0.05). Christensenellaceae_R-7_group was negatively correlated with the HAMD-17 score (P<0.01). CONCLUSION: Patients with subthreshold depression have dysbiosis of intestinal flora, and umbilical moxibustion may exert therapeutic effect by regulating the abundance and diversity of intestinal flora, increasing beneficial bacteria, and reducing harmful bacteria.

Predictive model for postpartum hemorrhage requiring hysterectomy in a minority ethnic region.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality, and hysterectomy is an important intervention for managing intractable PPH. Accurately predicting the need for hysterectomy and taking proactive emergency measures is crucial for reducing mortality rates. AIM: To develop a risk prediction model for PPH requiring hysterectomy in the ethnic minority regions of Qiandongnan, China, to help guide clinical decision-making. METHODS: The study included 23490 patients, with 1050 having experienced PPH and 74 who underwent hysterectomies. The independent risk factors closely associated with the necessity for hysterectomy were analyzed to construct a risk prediction model, and its predictive efficacy was subsequently evaluated. RESULTS: The proportion of hysterectomies among the included patients was 0.32% (74/23490), representing 7.05% (74/1050) of PPH cases. The number of deliveries, history of cesarean section, placenta previa, uterine atony, and placenta accreta were identified in this population as independent risk factors for requiring a hysterectomy. Receiver operating characteristic curve analysis of the prediction model showed an area under the curve of 0.953 (95% confidence interval: 0.928-0.978) with a sensitivity of 90.50% and a specificity of 90.70%. CONCLUSION: The model demonstrates excellent predictive power and is effective in guiding clinical decisions regarding PPH in the ethnic minority regions of Qiandongnan, China.

The successful use of rituximab in IgA nephropathy patients with podocytopathy: a case series.

Background: Immunoglobulin A nephropathy (IgAN) with podocytopathy is a rare pathological type of glomerular disease. The use of rituximab (RTX) in the treatment of glomerular diseases has increased in recent decades, but the efficacy of RTX in the treatment of patients with IgAN and podocytopathy has rarely been reported. Methods: This was a single-centre retrospective study of IgAN patients with podocytopathy who were treated with RTX as second-line therapy was conducted at our centre from 2019 to 2022. The aim of this study was to investigate the efficacy and safety of RTX in IgAN patients with podocytopathy. Results: Seven out of eight patients met the criteria for complete remission following RTX therapy. Only one patient experienced adverse events (infectious diarrhoea and pulmonary infection) and experienced relapse 6 months after RTX therapy. The maximum relapse-free time after RTX therapy was 20 months, while the maximum relapse-free time before RTX therapy was only 6 months. The number of relapses before RTX therapy (per year) was one to four; moreover, seven patients did not relapse and maintained remission at the last follow-up despite steroid withdrawal after RTX therapy. Conclusion: Overall, RTX effectively reduced proteinuria, increased the maximum relapse-free time, reduced the number of relapses per year and helped patients stop steroid use as soon as possible. RTX also helped most patients achieve clinical remission. RTX appears to be an effective and safe alternative for treating IgAN patients with podocytopathy with steroid dependence or frequent relapse.

Association of serum thyroid-stimulating hormone and bone mineral density in Chinese adults with normal thyroid function.

PURPOSE: This study aims to investigate the association of serum TSH with BMD in Chinese adults with normal thyroid function. METHODS: These participants were divided into tertiles based on serum TSH levels. Linear regression model and multinomial logistic regression models were used to analyze the associations of continuous BMD and categorical BMD with serum TSH, respectively. RESULTS: In women younger than 60 years, BMD decreased with the increase of TSH at normal level, while in women older than 60 years, BMD increased with the increase of TSH at normal level; besides, the BMD of women younger than 60 years old was significantly higher than that of women over 60 years old (156.05 ± 39.34 mg/cm3 vs. 86.95 ± 29.51 mg/cm3, P < 0.001). Linear regression results showed negative associations of BMD and normal TSH level in women with age younger than 60 years (ß=-4.34, P < 0.001), but this inverse trend was observed in women over 60 years old (ß = 2.04, P = 0.041). Both in men younger than 60 years and over 60 years old, BMD decreased with the increase of TSH at normal levels; besides, the BMD of men younger than 60 years was significantly higher than those over 60 years old (143.08 ± 32.76 mg/cm3 vs. 108.13 ± 31.99 mg/cm3, P < 0.001). CONCLUSIONS: The results demonstrated an opposite trend in BMD at normal TSH levels in younger and elder females, that is, in females younger than 60 years, BMD decreased with the increase of TSH, which indicated that TSH might play a different role in younger and elder females. However, this trend was not significant in males.

Correlation of psychological resilience with social support and coping style in Parkinson's disease: A cross-sectional study.

AIMS: To analyse the current status of psychological resilience in Parkinson's disease (PD) patients and its correlation with social support and coping style. DESIGN: A cross-sectional study. METHODS: PD patients hospitalized in a tertiary-level hospital in Shijiazhuang, Hebei Province, from March 2022 to March 2023 were selected for the study using the convenience sampling method. A general information questionnaire, psychological resilience scale, Medical Coping Modes Questionnaire and Perceived Social Support Scale were used to investigate 111 cases of PD. SPSS 25.0 software was used for statistical analysis. The data were analysed using independent samples t-test, one-way ANOVA, multiple linear regression analysis and the Pearson correlation coefficient. RESULTS: Parkinson's disease patients have a moderate level of psychological resilience. The results of the Pearson correlation analyses showed that the level of psychological resilience was positively correlated with social support and confrontation and was negatively correlated with avoidance and acceptance-resignation. The results of multiple linear regression analysis showed that social support and acceptance-resignation were the influencing factors of psychological resilience in PD patients. CONCLUSION: The psychological resilience of PD patients is at a moderate level. Social support and acceptance-resignation are the factors influencing the psychological resilience of PD patients. IMPACT STATEMENT: This study analysed the level of psychological resilience in PD patients and its correlation with social support and coping style from the perspective of positive psychology to provide some reference for targeted clinical interventions. Our study found that social support and acceptance-resignation are influential factors in psychological resilience in PD patients. Medical staff should encourage patients to face the disease positively and their social support should be increased in order to improve their level of psychological resilience. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A data-driven Bayesian network of management and organizational factors for human reliability analysis in the process industry.

According to historical statistical data, management and organizational factors (MOFs) contribute more to process accidents than technique factors. Under the umbrella of socio-tech system theory, human reliability analysis (HRA) has become a critical part of systemic probability risk analysis. In many HRA techniques, MOFs are among the performance shaping factors (PSFs). However, the interactions and causality of MOFs to human errors are still difficult to quantify and lack validation. To fill these gaps, a framework is proposed, considering data source selection, CBN construction algorithm comparison, and results validation. The case study employed the open access eMARS database as a data source. The optimized hybrid structure learning algorithm and Bayesian criteria parameter learning algorithm are employed to build a Causal Bayesian Network (CBN) of (MOFs) that lead to human error. The proposed kernel CBN is validated through prediction accuracy and sensitivity analysis. For theoretical contribution, the validated kernel BN could generally serve as the heart part of more specific CBNs as a basis for future works. For practical applications, an application shows the model's ability to quantify the contribution of MOFs to system reliability. The results show that human-machine interacting system reliability is most sensitive to organizational factors such as adequate training and procedures.