Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer.

BACKGROUND: The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. AIM: To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. METHODS: Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. RESULTS: One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). CONCLUSION: TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.

BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

Managing immune checkpoint inhibitor-associated gastritis: Insights and strategies.

Immune checkpoint inhibitors (ICIs) are widely used due to their effectiveness in treating various tumors. Immune-related adverse events (irAEs) are defined as adverse effects resulting from ICI treatment. Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects, such as diarrhea and colitis, which may lead to the discontinuation of ICIs.

Oral behaviors and anxiety are significant predictors of jaw function limitation in patients with anterior disc displacement without reduction.

OBJECTIVE: We aimed to describe jaw function characteristics in patients with anterior disc displacement without reduction (ADDWoR) using the jaw function limitation scale (JFLS), and to investigate the effects of biopsychosocial risk factors on limited jaw function. DESIGN: In this cross-sectional study of 636 patients with ADDWoR (females, 568; males, 68), we used the JFLS to assess jaw function. Behavioral, psychological, sociodemographic, and biomedical data were collected. Multivariate logistic regression analysis was used to determine risk factors affecting limited jaw function. A receiver operating characteristic curve was used to evaluate the predictive effect of these risk factors. RESULTS: ADDWoR-associated limitations included restricted jaw mobility and mastication, which exceeded median global functional limitations scale scores, especially mouth opening to bite an apple and chewing tough food. Females had greater limitations in jaw mobility, verbal and emotional communication, and overall. Multivariate logistic regression analysis findings indicated that oral behaviors, anxiety, sex, pain intensity, and maximal mouth opening (MMO) were predictive of limited jaw function (area under the curve, 72 %). CONCLUSION: Patients with ADDWoR reported mastication and jaw mobility restrictions, with females having more pronounced limitations, and specific risk factors identified as significant predictors of jaw function limitations. Along with pain relief and improvement in MMO, appropriate psychological counseling and oral behavioral correction facilitates recovery of jaw function in such patients.

Machine learning for high-precision simulation of dissolved organic matter in sewer: Overcoming data restrictions with generative adversarial networks.

Understanding the transformation process of dissolved organic matter (DOM) in the sewer is imperative for comprehending material circulation and energy flow within the sewer. The machine learning (ML) model provides a feasible way to comprehend and simulate the DOM transformation process in the sewer. In contrast, the model accuracy is limited by data restriction. In this study, a novel framework by integrating generative adversarial network algorithm-machine learning models (GAN-ML) was established to overcome the drawbacks caused by the data restriction in the simulation of the DOM transformation process, and humification index (HIX) was selected as the output variable to evaluate the model performance. Results indicate that the GAN algorithm's virtual dataset could generally enhance the simulation performance of regression models, deep learning models, and ensemble models for the DOM transformation process. The highest prediction accuracy on HIX (R2 of 0.5389 and RMSE of 0.0273) was achieved by the adaptive boosting model which belongs to ensemble models trained by the virtual dataset of 1000 samples. Interpretability analysis revealed that dissolved oxygen (DO) and pH emerge as critical factors warranting attention for the future development of management strategies to regulate the DOM transformation process in sewers. The integrated framework proposed a potential approach for the comprehensive understanding and high-precision simulation of the DOM transformation process, paving the way for advancing sewer management strategy under data restriction.

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: We aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR≤0.4, and sLNR>0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate and high SHLN metastasis burden groups (LMB, MMB and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Liver X receptor inverse agonist SR9243 attenuates rheumatoid arthritis via modulating glycolytic metabolism of macrophages.

Liver X receptors (LXRs) which link lipid metabolism and inflammation, were overexpressed in experimental rheumatoid arthritis (RA) rats as observed in our previous studies, while suppression of LXRα by silybin ameliorates arthritis and abnormal lipid metabolism. However, the role of LXRs in RA remains undefined. In this study, we investigated the inhibition role of LXRs in the polarization and activation of M1 macrophage by using a special LXRs inverse agonist SR9243, which led to ameliorating the progression of adjuvant-induced arthritis (AIA) in rats. Mechanistically, SR9243 disrupted the LPS/IFN-γ-induced Warburg effect in M1 macrophages, while glycolysis inhibitor 2-DG attenuated the inhibition effect of SR9243 on M1 polarization and the cytokines expression of M1 macrophages including iNOS, TNF-α, and IL-6 in vitro. Furthermore, SR9243 downregulated key glycolytic enzymes, including LDH-A, HK2, G6PD, GLUT1, and HIF-1α in M1 macrophages, which is mediated by increased phosphorylation of AMPK (Thr172) and reduced downstream phosphorylation of mTOR (Ser2448). Importantly, gene silencing of LXRs compromises the inhibition effect of SR9243 on M1 macrophage polarization and activation. Collectively, for the first time, our findings suggest that the LXR inverse agonist SR9243 mitigates adjuvant-induced rheumatoid arthritis and protects against bone erosion by inhibiting M1 macrophage polarization and activation through modulation of glycolytic metabolism via the AMPK/mTOR/HIF-1α pathway.

Association of serum pertussis antibodies with acute asthma attacks in children.

Objective: The aim of this study was to examine the serum antibody levels against pertussis toxin (PT) in children experiencing an acute asthma attack and to explore the potential association between these levels and asthma. Methods: A prospective investigation was conducted, which involved 107 children with acute asthma attacks and 77 children diagnosed with bronchitis. The serum immunoglobulin G (IgG) antibody levels specific to PT were measured by using an in-house enzyme-linked immunosorbent assay. Based on the serum PT-IgG antibody levels, the children with asthma were categorized into three groups: non-pertussis infected, suspected pertussis infected, and recent pertussis infected. The clinical manifestations and pulmonary function of pediatric patients diagnosed with asthma were assessed and compared across various groups. Results: Of the total asthma group, 25 patients tested positive for PT-IgG, whereas only six patients in the bronchitis group were PT-IgG positive. The prevalence of recent pertussis infection was observed to be higher in the asthma group compared with the bronchitis group. Within the asthma group, those with recent pertussis infection exhibited a higher likelihood of experiencing wheezing and impaired lung function in comparison with the non-pertussis infection group. Conclusion: Pertussis infection is relatively common in children with asthma and correlates with the severity of asthma.

Pollen identification of three notorious illicit drug plants and its potential applications in forensic practice.

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

Analysis of an adult diabetes mellitus caused by a rare mutation of the gene: A case report.

BACKGROUND: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/. CASE SUMMARY: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes. CONCLUSION: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.

Development of a Humanized Antibody Targeting Extracellular HSP90α to Suppress Endothelial-Mesenchymal Transition-Enhanced Tumor Growth of Pancreatic Adenocarcinoma Cells.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α's ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Ovarian function in patients with systemic lupus erythematosus: Pathogenesis, drug application and prospective therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.