The immunoregulatory effects of total glucosides of paeony in autoimmune diseases.

Total glucoside of paeonia (TGP) and its main active ingredient paeoniflorin, extracted from the Chinese herb Paeonia Lactiflora Pallas, exhibit potent immunomodulatory effects. TGP has been shown to inhibit inflammatory responses and disease progression in experimental models of multiple autoimmune diseases (AIDs), including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, psoriasis, etc. TGP shows broad immunomodulatory effects on many immune cells such as T cells, macrophages, and dendritic cells, by regulating their activation, proliferation, differentiation, and production of effector molecules. Mechanistically, TGP modulates intracellular signaling transductions including JAK/STAT, NF-κB, MAPK, and PI3K/AKT/mTOR pathways. Moreover, TGP has been applied in the clinical treatment of various AIDs with satisfactory therapeutic outcomes and minor side effects. Thus, available studies have demonstrated that TGP and its bioactive constituents exhibit anti-inflammatory and immunomodulatory functions and may have extensive applications in the treatment of AIDs.

The FTO-CMPK2 Pathway in Fibroblast-like Synoviocytes Modulates Rheumatoid Arthritis Synovial Inflammation and Cartilage Homeostasis via mtDNA Regulation.

In rheumatoid arthritis (RA), a debilitating autoimmune disorder marked by chronic synovial inflammation and progressive cartilage degradation, fibroblast-like synoviocytes (FLS) are key pathogenic players. Current treatments targeting these cells are limited. Our study focused on the Fat Mass and Obesity-associated protein (FTO), known for its roles in cell proliferation and inflammatory response modulation, and its involvement in RA. We specifically examined the inflammatory regulatory roles of FTO and CMPK2, a mitochondrial DNA synthesis protein, in FLS. Utilizing a combination of in vitro and in vivo methods, including FTO inhibition and gene knockdown, we aimed to understand FTO's influence on RA progression and chondrocyte functionality. Our findings showed that increased FTO expression in RA synovial cells enhanced their proliferation and migration and decreased senescence and apoptosis. Inhibiting FTO significantly slowed the disease progression in our models. Our research also highlighted that the FTO-CMPK2 pathway plays a crucial role in regulating synovial inflammation through the mtDNA-mediated cGAS/STING pathway, affecting chondrocyte homeostasis. This study indicates that targeting the FTO-CMPK2 axis could be a promising new therapeutic strategy for managing RA.

Whether full-length IL-38 acts as a promoter or inhibitor in activating rheumatoid arthritis fibroblast-like synoviocytes depends on IL-1ß.

AIM: IL-38 is a recently discovered inflammatory factor that belongs to the IL-1 family and has full-length and truncated forms. Clinical findings demonstrated that serum IL-38 levels in people with infectious and autoimmune diseases are significantly different from those in healthy people, but the form remains unclear. We are keenly interested in learning more about the regulatory role of full-length IL-38 in rheumatoid arthritis (RA), a classic autoimmune disease. METHODS: RA-fibroblast-like synoviocytes (RA-FLS) were isolated from six RA patients and stimulated with full-length IL-38 to observe IL-6 and IL-8 secretion. Then, the migration and invasion functions of FLS were assessed. Next, the protein expressions of the MAPK, NF-κB, and JAK pathways were evaluated. In addition, we examined the effect of full-length IL-38 on FLS functions in the presence of IL-1ß. The function of FLS affected by full-length IL-38 was also examined after blocking IL-1 and IL-36 receptors. RESULTS: The functions of FLS were activated after the cells were stimulated with full-length IL-38. IL-6 and IL-8 levels increased with an increase in the full-length IL-38 concentration, and full-length IL-38 induced the acceleration of FLS migration and invasion functions. In addition, the levels of proteins in the MAPK signaling pathway increased after stimulation with full-length IL-38 and depended on its concentration. However, when the FLS were stimulated by IL-38 and IL-1ß simultaneously, all experiments generated opposite results. Full-length IL-38 inhibited FLS function in the presence of IL-1ß. IL-1R and IL-36R blockers terminated all effects of full-length IL-38 on RA-FLS. CONCLUSION: Full-length IL-38 activates FLS functions and acts as a promoter in RA, whereas it inhibits FLS functions and acts as an inhibitor of RA in the presence of IL-1ß. The function of full-length IL-38 can be blocked by IL-1Ra and IL-36Ra.

Response to belimumab among patients with refractory lupus nephritis: a real-world observational retrospective multicenter study.

OBJECTIVES: Belimumab is a biological agent approved for the treatment of active lupus nephritis (LN), but its efficacy on refractory lupus nephritis (LN) is unknown. This study aims to evaluate the efficacy and safety of belimumab in Chinese patients with refractory LN. METHODS: This multicenter, observational, and retrospective study enrolled patients with refractory LN who failed induction therapy with steroids, cyclophosphamide, mycophenolate, and calcineurin inhibitors and received 24-week belimumab treatment before data analysis. Treatment outcomes include the overall clinical response (physician judgment, disease activity, organ damage) and renal response (complete renal response, partial renal response, no renal response). Laboratory indices and adverse events were recorded as well. RESULTS: Of the 45 patients enrolled in the study, 6 (13.3%) achieved complete renal response, 19 (42.2%) achieved partial renal response, and the overall renal response rate was 55.6%. Median rSLEDAI decreased from 12 (IQR 8-12) at baseline to 8 (IQR 4-8) (p < 0.0001), 4 (IQR 4-8) (p < 0.0001) at 12 and 24 weeks. Mean urinary protein decreased more than 50% from 3.2 g/24 h at baseline to 1.0 g/24 h at 24 weeks (p < 0.0001). The conditions of hypoalbuminemia and hypocomplementemia had also gradually improved. The levels of autoantibodies showed a significant downward trend. Additionally, 9 (20.0%) patients successfully reduced the dosage of prednisone to a safe range, and 3 of them achieved their treatment goal of prednisone cessation. The mean prednisone dosage decreased from 32.7 mg/day at baseline to 18.6 mg/day (p < 0.0001), 13.3 mg/day (p < 0.0001) at 12 and 24 weeks. There were 3 adverse events reported, including 2 cases of infection, and 1 case of allergy. No serious events occurred during the follow-up. CONCLUSIONS: Belimumab is effective and safe when used in clinical practice, which can be considered as an add-on therapy for refractory LN. Key Points • A multicenter observational study in the real clinical settings of China. • First revealed the efficacy and safety of belimumab in Chinese patients with refractory LN.

Mechanisms of Traditional Chinese medicine/natural medicine in HR-positive Breast Cancer: A comprehensive Literature Review.

ETHNOPHARMACOLOGICAL RELEVANCE: With the emergence of endocrine resistance, the survival and good prognosis of HR-positive breast cancer (HR + BC) patients are threatened. As a common complementary and alternative therapy in cancer treatment, traditional Chinese medicine (TCM) has been widely used, and its internal mechanisms have been increasingly explored. AIM OF THE REVIEW: In this review, the development status and achievements in understanding of the mechanisms related to the anti-invasion and anti-metastasis effects of TCM against HR + BC and the reversal of endocrine drug resistance by TCM in recent years have been summarized to provide ideas for antitumour research on the active components of TCM/natural medicine. METHODS: We searched the electronic databases PubMed, Web of Science, and China National Knowledge Infrastructure database (CNKI) (from inception to July 2023) with the key words "HR-positive breast cancer" or "HR-positive breast carcinoma", "HR + BC" and "traditional Chinese medicine", "TCM", or "natural plant", "herb", etc., with the aim of elucidating the intrinsic mechanisms of traditional Chinese medicine and natural medicine in the treatment of HR + BC. RESULTS: TCM/natural medicine monomers and formulas can regulate the expression of related genes and proteins through the PI3K/AKT, JAK2/STAT3, MAPK, Wnt and other signalling pathways, inhibit the proliferation and metastasis of HR + BC tumours, play a synergistic role in combination with endocrine drugs, and reverse endocrine drug resistance. CONCLUSION: The wide variety of TCM/natural medicine components makes the research and development of new methods of TCM for BC treatments more selective and innovative. Although progress has been made on research on TCM/natural medicine, there are still many problems in clinical and basic experimental designs, and more in-depth scientific explorations and research are still needed.

Compounds targeting ferroptosis in breast cancer: progress and their therapeutic potential.

In recent years, there has been a significant increase in the incidence of Breast cancer (BC), making it the most common cancer among women and a major threat to women's health. Consequently, there is an urgent need to discover new and effective strategies for treating BC. Ferroptosis, a novel form of cell death characterized by the accumulation of iron-dependent lipid reactive oxygen species, has emerged as a distinct regulatory pathway separate from necrosis, apoptosis, and autophagy. It is widely recognized as a crucial factor in the development and progression of cancer, offering a promising avenue for BC treatment. While significant progress has been made in understanding the mechanisms of ferroptosis in BC, drug development is still in its early stages. Numerous compounds, including phytochemicals derived from dietary sources and medicinal plants, as well as synthetic drugs (both clinically approved medications and laboratory reagents), have shown the ability to induce ferroptosis in BC cells, effectively inhibiting tumor growth. This comprehensive review aims to examine in detail the compounds that target ferroptosis in BC and elucidate their potential mechanisms of action. Additionally, the challenges associated with the clinical application of ferroptosis-inducing drugs are discussed, offering valuable insights for the development of novel treatment strategies for BC.

Comparison of anti-thymocyte globulin-based immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation in patients with transfusion-dependent non-severe aplastic anaemia: a retrospective study from a single centre.

OBJECTIVES: The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA. METHODS: Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors. RESULTS: A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p < 0.05), but not in five-year overall survival (OS) and event-free survival (EFS). Multivariate Cox regression analysis identified the transfusion of ≥78.75 units of red blood cells (RBCs) as the sole independent risk factor for OS (HR: 17.04, p = 0.039) in the IST group. For the HSCT group, disease duration (DD) ≥20 months and transfusion of ≥78.75 units of RBCs predicted an adverse EFS. Frontline IST exhibited superior 12-month ORR (68.8% vs 18.2%, p = 0.018) and five-year EFS when compared to non-frontline. Patients with a DD ranging from 6 to 20 months displayed a better EFS (p = 0.016) in HSCT group than those in the ATG-based IST group. CONCLUSIONS: Prior treatment history, disease duration, and serum ferritin levels should be carefully weighed when making the choice between ATG-based IST and allo-HSCT for TD-NSAA.

The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) present notable clinical challenges for individuals with transfusion-dependent non-severe aplastic anaemia (TD-NSAA).In terms of treatment outcomes, allo-HSCT exhibited a higher 12-month overall response rate (ORR) in comparison to ATG-based IST among TD-NSAA patients. Nevertheless, comparable rates of 5-year overall survival (OS) and event-free survival (EFS) were observed between the two therapeutic approaches.Several factors warrant consideration when deliberating between ATG-based IST and allo-HSCT for TD-NSAA. These factors include the patient's prior treatment history, disease duration, number of packed red cell transfusions received, and serum ferritin levels.

In-situ synthesis of magnetic iron-chitosan-derived biochar as an efficient persulfate activator for phenol degradation.

Persulfate activation is a forceful method for eliminating organic pollutants from coal chemical wastewater. In this study, an in-situ synthesis method was used to fabricate an iron-chitosan-derived biochar (Fe-CS@BC) nanocomposite catalyst using chitosan as a template. Fe was successfully imprinted into the newly synthesized catalyst. The Fe-CS@BC can activate persulfate to effectively degrade phenol. This point was confirmed by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The impact of various parameters on the removal rate was investigated in a single factor experiment. In Fe-CS@BC/PDS system, 95.96% of phenol (significantly higher than the original biochar of 34.33%) was removed within 45 min and 54.39% TOC within 2 h. The system showed superior efficiency over a broad pH value band from 3 to 9 and has a high degradation rate at ambient temperature. Free radical quenching experiment, EPR experiment and LSV experiment confirmed that multiple free radicals (including 1O2, SO4•-, O2•- and •OH) and electron transfer pathway combined to enhance phenol decomposition. Finally, the activation mechanism of persulfate by Fe-CS@BC was proposed to provide logical guidance on the treatment of organic pollutants in coal chemical wastewater.

Potential risk of tamoxifen: gut microbiota and inflammation in mice with breast cancer.

Objective: Tamoxifen is an effective anti-tumor medicine, but evidence has been provided on tamoxifen-related inflammation as well as its impact on gut microbiota. In this study, we aimed to investigate tamoxifen-induced gut microbiota and inflammation alteration. Methods: We established a BC xenograft mouse model using the MCF-7 cell line. 16S rRNA gene sequencing was used to investigate gut microbiota. qRT-PCR, western blotting, and cytometric bead array were used to investigate inflammation-related biomarkers. Various bioinformatic approaches were used to analyze the data. Results: Significant differences in gut microbial composition, characteristic taxa, and microbiome phenotype prediction were observed between control, model, and tamoxifen-treated mice. Furthermore, protein expression of IL-6 and TLR5 was up-regulated in tamoxifen-treated mice, while the mRNA of Tlr5 and Il-6, as well as protein expression of IL-6 and TLR5 in the model group, were down-regulated in the colon. The concentration of IFN-γ, IL-6, and IL12P70 in serum was up-regulated in tamoxifen-treated mice. Moreover, correlation-based clustering analysis demonstrated that inflammation-negatively correlated taxa, including Lachnospiraceae-UCG-006 and Anaerotruncus, were enriched in the model group, while inflammation-positively correlated taxa, including Prevotellaceae_UCG_001 and Akkermansia, were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice. Conclusion: Tamoxifen treatment significantly altered gut microbiota and increased inflammation in the breast cancer xenograft mice model. This may be related to tamoxifen-induced intestinal epithelial barrier damage and TLR5 up-regulation.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Chitin-derived biochar with nitrogen doping to activate persulfate for phenol degradation: Application potential and electron transfer pathway in system.

The fast and efficient removal of organic pollutants (e.g., phenolics) remains one of the focus problems in environment pollution. Thus, a chitin-derived biochar with nitrogen doping (N-BC) was successfully prepared at a lower calcination temperature of 600 °C, which is environmentally friendly and energy saving. The N-BC was analyzed by SEM, FTIR, BET, XRD, XPS and Raman spectroscopy to confirm that the doping of nitrogen element provided sufficient defect sites to promote the activation of persulfate (PDS). Quenching experiments and EPR results revealed the presence of •OH and •O2- contributed to phenol degradation in N-BC 600/PDS system. In addition, the linear sweep voltammogram experiments also demonstrated the existence of electron transfer pathway. The electrons were donated from phenol and shifted to PDS through N-BC. The graphitic N and carbon defects in N-BC served as the active sites of the reaction and involved absorption and transfer of electrons as the key character. Moreover, the removal rates of phenol and TOC reached 98.8% and 58.2% within 2 h, indicating that N-BC effectively activated the persulfate to degrade phenol. This study provides the theoretical support and potential applications for the activation of persulfate by nitrogen-doped biochar to degrade other phenolic compounds.

A Novel Functionalized MoS2-Based Coating for Efficient Solar Desalination.

Molybdenum disulfide (MoS2) has emerged as a promising photothermal material for solar desalination. However, its limitation in integrating with organic substances constrains its application because of the lack of functional groups on its surface. Here, this work presents a functionalization approach to introduce three different functional groups (-COOH -OH -NH2) on the surface of MoS2 by combining them with S vacancies. Subsequently, the functionalized MoS2 was coated on the polyvinyl alcohol-modified polyurethane sponge to fabricate a MoS2-based double-layer evaporator through an organic bonding reaction. Photothermal desalination experiments show that the functionalized material has higher photothermal efficiency. The evaporation rate of the hydroxyl functionalized the MoS2 evaporator evaporation rate is 1.35 kg m-2 h-1, and the evaporation efficiency is 83% at one sun. This work provides a new strategy for efficient, green, and large-scale utilization of solar energy by MoS2-based evaporators.

Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study.

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell-transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).

USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ.

The balance between inflammatory T helper type 17 (Th17) and immunosuppressive regulatory T (Treg) cells is critical for maintaining immune homeostasis in the human body and is tightly regulated under healthy conditions. An increasing number of studies have reported that deubiquitinases (DUBs) play a vital role in regulating Th17- and Treg-cell differentiation. However, the biological functions of only a small fraction of DUBs in Th17- and Treg-cell differentiation are well defined. In this study, we identified ubiquitin-specific peptidase 1 (USP1) as a vital regulator of CD4+ T-cell differentiation. USP1 promoted Th17-cell differentiation but attenuated Treg-cell differentiation, thereby promoting the development of inflammatory diseases. Mechanistically, USP1 in CD4+ T cells enhanced the activity of RORγt but promoted the proteasomal degradation of Foxp3 through deubiquitination and stabilization of TAZ in vitro and in vivo. Notably, ML323, a specific inhibitor of the USP1/UAF1 deubiquitinase complex, inhibited Th17-cell differentiation and promoted Treg-cell differentiation in vitro and in vivo, indicating that ML323 might be a promising candidate for the treatment of diseases associated with an imbalance between Th17 and Treg cells. Our study highlights the critical role of USP1 in regulating adaptive immune responses and suggests that USP1 might be a drug target for the treatment of diseases associated with an imbalance between Th17 and Treg cells.

Bioinformatic identification and validation of autophagy-related genes in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by progressive synovial inflammation and joint destruction, with a largely unknown etiology. Studies have suggested that autophagy and its expression may be involved in the pathogenesis of RA; however, autophagy-related genes in RA are still largely unidentified. Therefore, in this study, we aimed to identify and validate autophagy-related genes in RA. METHODS: We identified differentially expressed autophagy-related genes between patients with RA and healthy individuals using gene expression profiles in the GSE55235 dataset and R software. Subsequently, correlation analysis, protein-protein interaction, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using these differentially expressed autophagy-related genes. Finally, our results were validated by examining the expression of differentially expressed autophagy-related hub genes in clinical samples using qRT-PCR. RESULTS: We identified 52 potential autophagy-related genes in RA based on bioinformatic analyses. Ten hub genes, CASP8, CTSB, TNFSF10, FADD, BAX, MYC, FOS, CDKN1A, GABARAPL1, and BNIP3, were validated to be differentially expressed and may serve as valuable prognostic markers and new potential therapeutic targets for RA via the regulation of autophagy. CONCLUSIONS: Our results may help improve the understanding of RA pathogenesis. Autophagy-related genes in RA could be valuable biomarkers for diagnosis and prognosis and they might be exploited clinically as therapeutic targets in the future.

Diethyldithiocarbamate inhibits the activation of hepatic stellate cells via PPARα/FABP1 in mice with non-alcoholic steatohepatitis.

Activation of hepatic stellate cells (HSCs) is the main course of liver fibrosis which is positively correlated with adverse clinical outcomes in non-alcoholic steatohepatitis (NASH). Diethyldithiocarbamate (DDC) attenuates NASH related liver fibrosis in mice, but its underlying mechanisms remains unclear. In this study, the data showed that DDC inhibited the activation of HSCs in high fat choline-deficient, L-amino acid-defined (CDAA) diet induced NASH. Double Immunofluorescence analysis showed that the baseline expression of peroxisome proliferator-activated receptor α (PPARα) is high in HSCs in normal mouse liver and notably decreases in the NASH liver, indicating that PPARα might be associated with the activation of HSCs. While, DDC upregulated PPARα in HSCs in the NASH liver. Mixture of free fatty acid was used to induce steatosis of hepatocytes. Human HSCs (LX-2 cells) were activated after co-cultured with steatotic hepatocytes, and DDC inhibited the activation of LX-2 cells. Meanwhile, DDC upregulated PPARα and FABP1, and promoted the accumulation of LDs in LX-2 cells. PPARα small interfering RNA blocked these effect of DDC. These findings suggest that PPARα is associated with the activation of HSCs in the context of NASH. DDC improves NASH related fibrosis through inhibiting the activation of HSCs via PPARα/FABP1.

The expression of androgen receptor in triple-negative breast cancer and the effect of a traditional Chinese medicine formula on disease-free survival.

Background: Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC. Methods: The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t-test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data. Results: We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group. Conclusions: The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects.

Efficacy and safety of microwave ablation for benign breast lesions: a systematic review and meta-analysis.

Aim: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of microwave ablation (MWA) for benign breast lesions. Material and methods: PubMed, Embase, Web of Science, Cochrane Library databases, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform databases were searched. Results: A total of 10 studies were included, giving a sample size of 1241 patients and 2729 benign breast lesions. The first complete ablation success rate was 96%. The volume reduction ratio (VRR) after 3/6/12 months was 47.4%, 62.1%, and 85.8%, respectively. After 12 months, the lesion disappearance rate was 53.6%, and the efficiency rate was 99%. The rate of excellent cosmesis was 88% and the rate of good cosmesis was 10%. The complication rate was 2%. Conclusions: MWA is safe and effective for treating benign breast lesions. It can be a promising minimally invasive choice for benign breast lesions.

The preventive and therapeutic effects of probiotics on mastitis: A systematic review and meta-analysis.

Acute mastitis is one of the main reasons why breastfeeding women stop breastfeeding, and medication should be used with caution. Considering the uncertainty of mastitis infection and the indications of antibiotic use, as well as the problem of drug resistance and the safety of medication during lactation, probiotics have become an alternative treatment choice. However, a meta-analysis of the effects of probiotics in preventing and treating lactational mastitis is still lacking. Therefore, we searched six electronic databases and the sites of clinical trial registration, a total of six randomized controlled trials were included in this meta-analysis, which showed that oral probiotics during pregnancy can reduce the incidence of mastitis (RR: 0.49, 95% CI: 0.35 to 0.69; p<0.0001). After oral administration of probiotics, the counts of bacteria in the milk of healthy people and mastitis patients were both significantly reduced (in healthy people: MD: -0.19, 95% CI: -0.23 to -0.16, p<0.00001; in mastitis patients: MD: -0.89, 95% CI: -1.34 to -0.43, p = 0.0001). These indicate that to a certain extent, probiotics are beneficial in reducing the incidence rate of mastitis during lactation and some related mastitis symptoms. However, high-quality multicenter clinical trials are still needed to support this result.

Etanercept/celecoxib on improving MRI inflammation of active ankylosing spondylitis: A multicenter, open-label, randomized clinical trial.

Objective: To investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active ankylosing spondylitis (AS) patients with etanercept and celecoxib alone/combined treatment. Methods: A randomized controlled trial was conducted in three medical centers in China. Adult AS patients with BASDAI ≥4 or ASDAS ≥2.1, CRP >6 mg/L, or ESR 28 mm/1st hour were randomly assigned (1:1:1 ratio) to celecoxib 200 mg bid or etanercept 50 mg qw or combined therapy for 52 weeks. The primary outcomes were SPARCC change of the sacroiliac joint (SIJ) and spine and the proportion of patients achieving ASAS20 response at 52 weeks. Results: Between September 2014 and January 2016, we randomly assigned 150 patients (mean age, 32.4 years; mean disease duration, 109 months), and 133 (88.6%) completed the study. SPARCC inflammation scores of the SIJ and spine decreased in the three groups, and significant differences were found between the combined group and the celecoxib group [between-group difference: -6.33, 95% CI (-10.56, -2.10) for SIJ; -9.53, 95% CI (-13.73, -5.33) for spine] and between the etanercept group and the celecoxib group [between-group difference: -5.02, 95% CI (-9.29, -0.76) for SIJ; -5.80, 95% CI (-10.04, -1.57) for spine]. The ASAS20 response rates were 44%, 58%, and 84% in the celecoxib, etanercept, and combined groups, respectively, and a significant difference was only found between the combined and the celecoxib groups. Conclusion: Etanercept with or without celecoxib decreases inflammation detected by MRI at 1 year compared to celecoxib alone in active AS patients. The combination of etanercept and celecoxib was superior to celecoxib alone for the primary clinical response. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01934933.