Effects of flora deficiency on the structure and function of the large intestine.

The significant anatomical changes in large intestine of germ-free (GF) mice provide excellent material for understanding microbe-host crosstalk. We observed significant differences of GF mice in anatomical and physiological involving in enlarged cecum, thinned mucosal layer and enriched water in cecal content. Furthermore, integration analysis of multi-omics data revealed the associations between the structure of large intestinal mesenchymal cells and the thinning of the mucosal layer. Increased Aqp8 expression in GF mice may contribute to enhanced water secretion or altered hydrodynamics in the cecum. In addition, the proportion of epithelial cells, nutrient absorption capacity, immune function and the metabolome of cecum contents of large intestine were also significantly altered. Together, this is the first systematic study of the transcriptome and metabolome of the cecum and colon of GF mice, and these findings contribute to our understanding of the intricate interactions between microbes and the large intestine.

CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

Probing long-lived radioactive isotopes on the double-logarithmic Segrè chart.

Isotopes have been widely applied in a variety of scientific subjects; many aspects of isotopes, however, remain not well understood. In this study, I investigate the relation between the number of neutrons (N) and the number of protons (Z) in stable isotopes of non-radioactive elements and long-lived isotopes of radioactive elements at the double-linear scale (conventional Segrè chart) and the double-logarithmic scale. Statistical analyses show that N is a power-law function of Z for these isotopes: N = 0.73 × Z 1.16. This power-law relation provides better predictions for the numbers of neutrons in stable isotopes of non-radioactive elements and long-lived isotopes of radioactive elements than the linear relation on the conventional Segrè chart. The power-law pattern reveled here offers empirical guidance for probing long-lived isotopes of unknown radioactive elements.

Indole-3-carboxaldehyde ameliorates ionizing radiation-induced hematopoietic injury by enhancing hematopoietic stem and progenitor cell quiescence.

Indole-3-carboxaldehyde (I3A), one of tryptophan metabolites derived from gut microbiota, extends the lifespan of mice after high-dose ionizing radiation exposure. Persistent myelosuppression is the most common and fatal complication for victims of nuclear accidents and patients undergoing radiotherapy, with few therapeutic options available. However, whether and how I3A protects ionizing radiation-induced hematopoietic toxicity remain unknown. In this study, we demonstrated that I3A treatment effectively ameliorated radiation-induced hematopoietic injury through accelerating peripheral blood cells recovery, promoting bone marrow cellularity restoration and enhancing functional HSPC regeneration. Additionally, I3A also suppressed intracellular reactive oxygen species production and inhibited apoptosis in irradiated HSPCs. Mechanistically, I3A treatment significantly increased HSPC quiescence, thus conferring HSPCs with resistance against radiation injury. Finally, I3A treatment could improve survival of lethally irradiated mice. Taken together, our data suggest that I3A acts as a gut microbiota-derived paracrine factor that regulates HSPC regeneration and may serve as a promising therapeutic agent for ionizing radiation-induced myelosuppression.

Sonosensitizer Nanoplatforms Augmented Sonodynamic Therapy-Sensitizing Shikonin-Induced Necroptosis Against Hepatocellular Carcinoma.

Background: Apoptosis resistance of hepatocellular carcinoma (HCC) often leads to treatment failure. Nonetheless, overcoming the resistance of HCC to apoptosis by inducing necroptosis of tumor cells to bypass the apoptotic pathway may be a promising treatment strategy. Sonodynamic therapy (SDT) has broad prospects in disease treatment because of its noninvasive characteristic and spatiotemporal control. The combination of SDT and shikonin in the treatment of HCC is expected to be a new tumor treatment method that can overcome apoptosis resistance. Methods: In this study, the antitumor effect was evaluated using normal liver cell line WRL68, HCC cell line HepG2 and HepG2 xenograft mouse models. Indocyanine green (ICG) was loaded on nanobubbles (NBs) to construct ICG-loaded nanobubbles (ICG-NBs). Combined sonosensitizer nanoplatforms with ultrasound (US) to achieve efficient SDT, the combination of SDT and shikonin in treating HCC can activate shikonin-induced necroptosis. As a result, tumor cells that produced apoptosis resistance were destroyed by necroptosis. Results: The results indicated a successful preparation of ICG-NBs with a uniform particle size of 273.0 ± 118.9 nm spherical structures. ICG-NB-mediated SDT, in combination with shikonin treatment, inhibited the viability, invasion, and migration of tumor cells. SDT + shikonin treatment group caused a substantial increase in necroptotic cells. The increased degree of tumor necrosis and the upregulated expression of receptor-interacting protein 3 kinase were observed in vivo studies, which indicated that the antitumor effect was accompanied by enhanced necroptosis in the SDT + shikonin treatment group. Conclusion: ICG-NB-mediated SDT combined with shikonin inhibits the growth of HCC by increasing the necroptosis of tumor cells. Therefore, this combination therapy is a promising treatment strategy against the specific cancer.

Sono-Immunotherapy Mediated Controllable Composite Nano Fluorescent Probes Reprogram the Immune Microenvironment of Hepatocellular Carcinoma.

Background: Despite the clinical efficacy of immunotherapy in treating malignant tumors, its effectiveness is often hampered by the immunosuppressive nature of the tumor microenvironment (TME). In this study, we propose the design of a nanoscale ultrasound contrast agent capable of triggering macrophage polarization and immunogenic cell death (ICD) for the treatment of hepatocellular carcinoma (HCC) through sonodynamic treatment (SDT) and immunotherapy. Methods: The re-educator (designated as ICG@C3F8-R848 NBs) is composed of the Toll-like receptor agonist resiquimod (R848) and the sonosensitizer Indocyanine green (ICG), utilizing nanobubbles (NBs) as carriers. The technique known as ultrasound-targeted nanobubble destruction (UTND) employs nanosized microbubbles and low-frequency ultrasound (LFUS) to ensure accurate drug delivery and enhance safety. Results: Following intravenous delivery, ICG@C3F8-R848 NBs have the potential to selectively target and treat primary tumors using SDT in conjunction with ultrasonography. Importantly, R848 can enhance antitumor immunity by inducing the polarization of macrophages from an M2 to an M1 phenotype. Conclusion: The SDT-initiated immunotherapy utilizing ICG@C3F8-R848 NBs demonstrates significant tumor suppression effects with minimal risk of systemic toxicity. The utilization of this self-delivery re-education technique would contribute to advancing the development of nanomedicine for the treatment of hepatocellular carcinoma.

Combination of thalidomide and Clostridium butyricum relieves chemotherapy-induced nausea and vomiting via gut microbiota and vagus nerve activity modulation.

Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and Clostridium butyricum. Our results suggested that the combination of THD and C. butyricum abundantly enhanced the anticancer effect of cisplatin via activating the caspase-3 apoptosis pathway, and also ameliorated CINV via inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HT3R and NK-1R) in brain and colon. Additionally, the combination of THD and C. butyricum reversed the gut dysbacteriosis in CRC mice by increasing the abundance of Clostridium, Lactobacillus, Bifidobacterium, and Ruminococcus at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1ß, and TNF-α. In all, these results suggest that the combination of THD and C. butyricum had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.

Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome.

BACKGROUND AND AIMS: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown. METHODS: HSOS model was established by gavage of monocrotaline (MCT) in rats. Fecal microbiota transplantation (FMT) with HSOS-derived or healthy gut flora was also conducted to validate the role of gut microflora in MCT-induced liver injury. The microbial 16 s rRNA analysis and untargeted metabolomics analysis in the faeces were performed to identify HSOS-related flora and metabolites. Finally, by supplementation with specific tryptophan metabolites, such as indole-3-acetaldehyde (IAAld) and indole acetic acid (IAA), we further confirmed the role of tryptophan metabolism in HSOS and the role of the AhR/Nrf2 pathway in MCT-induced liver injury. RESULTS: MCT induced HSOS-like liver injury in rats with significantly altered gut microbiota. Particularly, some tryptophan-metabolizing bacteria reduced in MCT-treated rats, such as Bacteroides, Bifidobacterium, Lactobacillus and Clostridium, and accompanied by a decrease in microbial tryptophan metabolic activity and a series of tryptophan derivatives. Restoring the gut microbiota via FMT improved MCT-induced liver damage, while HSOS-derived gut microbiota aggravated the liver injury induced by MCT. Supplementation with microbial tryptophan derivatives (IAAld or IAA), or 6-formylindolo(3,2-b)carbazole (Ficz, an AhR agonist) could activate the AhR/Nrf2 signaling pathway, thereby attenuating the MCT-induced liver oxidative stress and liver sinusoidal endothelial cells injury. CONCLUSIONS: Gut microbiota plays a critical role in MCT-induced HSOS, with inadequate microbial tryptophan metabolism in the gut and consequently a lower activity of the AhR/Nrf2 signaling pathway in the liver, which should be a potential target for the management of HSOS.

High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species.

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet (HFD)-associated metabolic disorders. However, the underlying mechanism remains elusive. In the present study, by comparing HFD- and normal diet (ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier. Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions, as confirmed by the increased reactive oxygen species (ROS) levels in fecal microbiota incubation in vitro and in the lumen, which were detected using in vivo fluorescence imaging. This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation (FMT) into germ-free (GF) mice, downregulating the gut barrier tight junctions. Similarly, mono-colonizing GF mice with an Enterococcus strain excelled in ROS production, damaged the gut barrier, induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells, and exacerbated fatty liver, compared with other low-ROS-producing Enterococcus strains. Oral administration of recombinant high-stability-superoxide dismutase (SOD) significantly reduced intestinal ROS, protected the gut barrier, and improved fatty liver against the HFD. In conclusion, our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

Early Prediction of Response to Neoadjuvant Chemotherapy Using Quantitative Parameters on Automated Breast Ultrasound Combined with Contrast-Enhanced Ultrasound in Breast Cancer.

OBJECTIVE: This prospective study was aimed at evaluating the role of automated breast ultrasound (ABUS) and contrast-enhanced ultrasound (CEUS) in the early prediction of treatment response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Forty-three patients with pathologically confirmed invasive breast cancer treated with NAC were included. The standard for evaluation of response to NAC was based on surgery within 21 d of completing treatment. The patients were classified as having a pathological complete response (pCR) and a non-pCR. All patients underwent CEUS and ABUS 1 wk before receiving NAC and after two treatment cycles. The rising time (RT), time to peak (TTP), peak intensity (PI), wash-in slope (WIS) and wash-in area under the curve (Wi-AUC) were measured on the CEUS images before and after NAC. The maximum tumor diameters in the coronal and sagittal planes were measured on ABUS, and the tumor volume (V) was calculated. The difference (∆) in each parameter between the two treatment time points was compared. Binary logistic regression analysis was used to identify the predictive value of each parameter. RESULTS: ∆V, ∆TTP and ∆PI were independent predictors of pCR. The CEUS-ABUS model achieved the highest AUC (0.950), followed by those based on CEUS (0.918) and ABUS (0.891) alone. CONCLUSION: The CEUS-ABUS model could be used clinically to optimize the treatment of patients with breast cancer.

Underwater instant adhesion mechanism of self-assembled amphiphilic hemostatic granular hydrogel from Andrias davidianus skin secretion.

The widespread use of biological tissue adhesives for tissue repair is limited by their weak adhesion in a wet environment. Herein, we report the wet adhesion mechanism of a dry granular natural bioadhesive from Andrias davidianus skin secretion (ADS). Once contacting water, ADS granules self-assemble to form a hydrophobic hydrogel strongly bonding to wet substrates in seconds. ADS showed higher shear adhesion than current commercial tissue adhesives and an impressive 72-h underwater adhesion strength of ∼47kPa on porcine skin tissue. The assembled hydrogel in water maintained a dissipation energy of ∼8 kJ/m3, comparable to the work density of muscle, exhibiting its robustness. Unlike catechol adhesion mechanism, ADS wet adhesion mechanism is attributed to water absorption by granules, and the unique equilibrium of protein hydrophobicity, hydrogen bonding, and ionic complexation. The in vivo adhesion study demonstrated its excellent wet adhesion and hemostasis performance in a rat hepatic and cardiac hemorrhage model.

Construction of a Humanized PBMC-PDX Model to Study the Efficacy of a Bacterial Marker in Lung Cancer Immunotherapy.

Commensal microbiome is a key factor of lung cancer immunotherapy efficacy. Elucidating the role of specific strains as bacterial markers in immunotherapy has drawn great attention from the academia. At present, most preclinical studies about the relationship between bacterial markers and immunotherapy rely on the syngeneic mouse models. However, mice differ greatly from humans in immune system and tumor characteristics. In this study, humanized mouse models based on peripheral blood mononuclear cells (PBMCs) immune reconstitution and lung cancer cell line-derived xenograft (CDX) or patient-derived xenograft (PDX) were constructed. The PBMC-PDX model was shown to be superior to the PBMC-CDX model in preserving tumor heterogeneity and construction time-saving. Through optimizing the experimental process, the time it took for humanized models to evaluate the effect of cancer treatment was reduced to 42 days. Next, by utilizing PBMC-PDX mice treated with antibiotics (ATB), the role of Bifidobacterium longum in lung cancer immunotherapy was studied. It was found that although both Bifidobacterium longum and immunotherapy drug pembrolizumab alone showed suppressing tumor growth, the efficacy of pembrolizumab was attenuated when administrated to mice colonized with Bifidobacterium longum. Further exploration revealed that Bifidobacterium longum caused significant changes in the proportion of human CD45+ cells in the PBMC-PDX model. The PBMC-PDX model has the potential to be applied as an efficient platform to support evaluation of bacterial markers in immunotherapy research and facilitate development of precision medicine targeting human commensal bacteria.

Prediction model of axillary lymph node status using automated breast ultrasound (ABUS) and ki-67 status in early-stage breast cancer.

BACKGROUND: Automated breast ultrasound (ABUS) is a useful choice in breast disease diagnosis. The axillary lymph node (ALN) status is crucial for predicting the clinical classification and deciding on the treatment of early-stage breast cancer (EBC) and could be the primary indicator of locoregional recurrence. We aimed to establish a prediction model using ABUS features of primary breast cancer to predict ALN status. METHODS: A total of 469 lesions were divided into the axillary lymph node metastasis (ALNM) group and the no ALNM (NALNM) group. Univariate analysis and multivariate analysis were used to analyze the difference of clinical factors and ABUS features between the two groups, and a predictive model of ALNM was established. Pathological results were as the gold standard. RESULTS: Ki-67, maximum diameter (MD), posterior feature shadowing or enhancement and hyperechoic halo were significant risk factors for ALNM in multivariate logistic regression analysis (P < 0.05). The four risk factors were used to build the predictive model, and it achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.791 (95% CI: 0.751, 0.831). The accuracy, sensitivity and specificity of the prediction model were 72.5%, 69.1% and 75.26%. The positive predictive value (PPV) and negative predictive value (NPV) were 66.08% and 79.93%, respectively. Distance to skin, MD, margin, shape, internal echo pattern, orientation, posterior features, and hyperechoic halo showed significant differences between stage I and stage II (P < 0.001). CONCLUSION: ABUS features and Ki-67 can meaningfully predict ALNM in EBC and the prediction model may facilitate a more effective therapeutic schedule.

Performance of novel deep learning network with the incorporation of the automatic segmentation network for diagnosis of breast cancer in automated breast ultrasound.

OBJECTIVE: To develop novel deep learning network (DLN) with the incorporation of the automatic segmentation network (ASN) for morphological analysis and determined the performance for diagnosis breast cancer in automated breast ultrasound (ABUS). METHODS: A total of 769 breast tumors were enrolled in this study and were randomly divided into training set and test set at 600 vs. 169. The novel DLNs (Resent v2, ResNet50 v2, ResNet101 v2) added a new ASN to the traditional ResNet networks and extracted morphological information of breast tumors. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic (ROC) curve (AUC), and average precision (AP) were calculated. The diagnostic performances of novel DLNs were compared with those of two radiologists with different experience. RESULTS: The ResNet34 v2 model had higher specificity (76.81%) and PPV (82.22%) than the other two, the ResNet50 v2 model had higher accuracy (78.11%) and NPV (72.86%), and the ResNet101 v2 model had higher sensitivity (85.00%). According to the AUCs and APs, the novel ResNet101 v2 model produced the best result (AUC 0.85 and AP 0.90) compared with the remaining five DLNs. Compared with the novice radiologist, the novel DLNs performed better. The F1 score was increased from 0.77 to 0.78, 0.81, and 0.82 by three novel DLNs. However, their diagnostic performance was worse than that of the experienced radiologist. CONCLUSIONS: The novel DLNs performed better than traditional DLNs and may be helpful for novice radiologists to improve their diagnostic performance of breast cancer in ABUS. KEY POINTS: • A novel automatic segmentation network to extract morphological information was successfully developed and implemented with ResNet deep learning networks. • The novel deep learning networks in our research performed better than the traditional deep learning networks in the diagnosis of breast cancer using ABUS images. • The novel deep learning networks in our research may be useful for novice radiologists to improve diagnostic performance.

Oxidative metabolisms catalyzed Earth's oxygenation.

The burial of organic carbon, which prevents its remineralization via oxygen-consuming processes, is considered one of the causes of Earth's oxygenation. Yet, higher levels of oxygen are thought to inhibit burial. Here we propose a resolution of this conundrum, wherein Earth's initial oxygenation is favored by oxidative metabolisms generating partially oxidized organic matter (POOM), increasing burial via interaction with minerals in sediments. First, we introduce the POOM hypothesis via a mathematical argument. Second, we reconstruct the evolutionary history of one key enzyme family, flavin-dependent Baeyer-Villiger monooxygenases, that generates POOM, and show the temporal consistency of its diversification with the Proterozoic and Phanerozoic atmospheric oxygenation. Finally, we propose that the expansion of oxidative metabolisms instigated a positive feedback, which was amplified by the chemical changes to minerals on Earth's surface. Collectively, these results suggest that Earth's oxygenation is an autocatalytic transition induced by a combination of biological innovations and geological changes.

Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Humans.

BACKGROUND: In the past few decades, nanomaterial-mediated phototherapy has gained significant attention as an alternative antitumor strategy. However, its antitumor success is majorly limited to the treatment of subcutaneous tumors in nude mice. In fact, no studies have been previously conducted in this area/field on clinically-relevant big animal models. Therefore, there is an urgent need to conduct further investigation in a typical big animal model, which is more closely related to the human body. RESULTS: In this study, niobium carbide (NbC) was selected as a photoactive substance owing to the presence of outstanding near-infrared (NIR) absorption properties, which are responsible for the generation of NIR-triggered hyperthermia and reactive oxygen species that contribute towards synergetic photothermal and photodynamic effect. Moreover, the present study utilized macrophages as bio-carrier for the targeted delivery of NbC, wherein phagocytosis by macrophages retained the photothermal/photodynamic effect of NbC. Consequently, macrophage-loaded NbC ensured/allowed complete removal of solid tumors both in nude mice and big animal models involving rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) were used to monitor physiological evolution in tumor in vivo post-treatment, which clearly revealed the occurrence of the photoablation process in tumor and provided a new strategy for the surveillance of tumor in big animal models. CONCLUSION: Altogether, the use of a large animal model in this study presented higher clinical significance as compared to previous studies.

RNA-Seq Explores the Mechanism of Oxygen-Boosted Sonodynamic Therapy Based on All-in-One Nanobubbles to Enhance Ferroptosis for the Treatment of HCC.

BACKGROUND: The combination of sonodynamic therapy and oxygenation strategy is widely used in cancer treatment. However, due to the complexity, heterogeneity and irreversible hypoxic environment produced by hepatocellular carcinoma (HCC) tissues, oxygen-enhancing sonodynamic therapy (SDT) has failed to achieve the desired results. With the emergence of ferroptosis with reactive oxygen species (ROS) cytotoxicity, this novel cell death method has attracted widespread attention. METHODS: In this study, nanobubbles (NBs) were connected with the sonosensitizer Indocyanine green (ICG) to construct a 2-in-1 nanoplatform loaded with RAS-selective lethal (RSL3, ferroptosis promoter) (RSL3@O2-ICG NBs), combined with oxygen-enhanced SDT and potent ferroptosis. In addition, nanobubbles (NBs) combined with low-frequency ultrasound (LFUS) are called ultrasound-targeted nanobubble destruction (UTND) to ensure specific drug release and improve safety. RESULTS: MDA/GSH and other related experimental results show that RSL3@O2-ICG NBs can enhance SDT and ferroptosis. Through RNA sequencing (RNA-seq), the differential expression of LncRNA and mRNA before and after synergistic treatment was identified, and then GO and KEGG pathways were used to enrich and analyze target genes and pathways related ferroptosis sensitivity. We found that they were significantly enriched in the ferroptosis-related pathway MAPK cascade and cell proliferation. Then, we searched for the expression of differentially expressed genes in the TCGA Hepatocellular carcinoma cohort. At the same time, we evaluated the proportion of immune cell infiltration and the identification of co-expression network modules and related prognostic analysis. We found that it was significantly related to the tumor microenvironment of hepatocellular carcinoma. The prognostic risk genes "SLC37A2" and "ITGB7" may represent new hepatocellular carcinoma ferroptosis-inducing markers and have guiding significance for treating hepatocellular carcinoma. CONCLUSION: The therapeutic effect of the in vitro synergistic treatment has been proven to be significant, revealing the prospect of 2-in-1 nanobubbles combined with SDT and ferroptosis in treating HCC.

The Interplay between Androgen and Gut Microbiota: Is There a Microbiota-Gut-Testis Axis.

The gut microbiota, a large ecosystem interacting with the host, has been shown to affect the health and fitness of the host-microbial superorganism. Increasing evidence suggests that the gut microbiota communicates with distal organs of the host including the brain, liver, and muscle, as well as testis, through various complex mechanisms. So far, we know that the androgen can markedly remodel the gut microbiota and has initiated an interdisciplinary field termed "microgenderome." More recently, the gut microbiota has been found as a major regulator of androgen production and metabolism in turn and even could trespass the blood-testis barrier (BTB) to regulate spermatogenesis, which largely updates the current knowledge on male reproduction. In this review, we provided a brief overview of the context of the gender bias of diseases related to gut microbiota, the sex dimorphism of gut microbiota, and their relationships with androgen. We also summarized the known interaction between the testis and gut microbiota based on published animal studies and tentatively discussed the hypothesis of microbiota-gut-testis axis. Finally, we highlighted the opportunities and challenges underlying the ongoing research. This knowledge may extend our understanding of the role of gut microbiota in male health and microbiota-related diseases.

Dependability of Automated Breast Ultrasound (ABUS) in Assessing Breast Imaging Reporting and Data System (BI-RADS) Category and Size of Malignant Breast Lesions Compared with Handheld Ultrasound (HHUS) and Mammography (MG).

PURPOSE: This study aimed to evaluate the dependability of automated breast ultrasound (ABUS) compared with handheld ultrasound (HHUS) and mammography (MG) on the Breast Imaging Reporting and Data System (BI-RADS) category and size assessment of malignant breast lesions. PATIENTS AND METHODS: A total of 344 confirmed malignant lesions were recruited. All participants underwent MG, HHUS, and ABUS examinations. Agreements on the BI-RADS category were evaluated. Lesion size assessed using the three methods was compared with the size of the pathological result as the control. Regarding the four major molecular subtypes, correlation coefficients between size on imaging and pathology were also evaluated. RESULTS: The agreement between ABUS and HHUS on the BI-RADS category was 86.63% (kappa = 0.77), whereas it was 32.22% (kappa = 0.10) between ABUS and MG. Imaging lesion size compared to pathologic lesion size was assessed correctly in 36.92%/52.91% (ABUS), 33.14%/48.84% (HHUS) and 33.44%/43.87% (MG), with the threshold of 3 mm/5 mm, respectively. The correlation coefficient of size of ABUS-Pathology (0.75, Spearman) was statistically higher than that of the MG-Pathology (0.58, Spearman) with P < 0.01, but not different from that of the HHUS-Pathology (0.74, Spearman) with P > 0.05. The correlation coefficient of ABUS-Pathology was statistically higher than that of MG-Pathology in the triple-negative subtype, luminal B subtype, and luminal A subtype (P<0.01). CONCLUSION: The agreement between ABUS and HHUS in the BI-RADS category was good, whereas that between ABUS and MG was poor. ABUS and HHUS allowed a more accurate assessment of malignant tumor size compared to MG.

The choice of operation timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) for acute cholecystitis: a retrospective clinical analysis.

BACKGROUND: This study aimed to evaluate the timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: Patients with acute moderate to severe cholecystitis treated by LC after PTGBD in the Department of Hepatobiliary and Pancreatic Surgery, Nankai Hospital (N-362) between January 2017 and August 2019were retrospectively enrolled into this study. According to the interval times from PTGBD to LC, the patients were divided into six groups, including group A (105 cases, within 1 week), group B (62 cases, 1-2 weeks), group C (34 cases, 3-4 weeks), group D (54 cases, 5-8 weeks), group E (24 cases, 9-12 weeks), and group F (83 cases, over 12 weeks). The gender, age, hospital stay, duration of operation, rate of conversion to laparotomy, incidence of complications, and hospitalization expenses of the six groups were evaluated and compared. RESULTS: Of the 362 cases of LC, 346 patients were operated successfully (95.6%), 10 were converted to laparotomy (2.8%), 16 had various complications (4.4%), and 2 died (0.6%). There were no significant differences between groups in the gender ratio, complication rate, and rate of conversion to laparotomy. The hospital stay and hospitalization expenses in group A were the least and significantly lower than those in other groups (P<0.01), and the duration of operation in group D was the longest and significantly higher than that in groups A, B, E, and F (P<0.05). CONCLUSIONS: For non-elderly patients diagnosed with acute moderate to severe cholecystitis with an anesthesia risk score [American Society of Anesthesiologists (ASA)] ≤2, LC is recommended to be performed within 1 week after PTGBD surgery. If delayed LC is performed within 2 to 8 weeks after PTGBD, the operation time will be longer due to inflammatory edema and fibrous adhesion of the gallbladder triangle. If PTGBD is performed for more than 2 months and the clinical circumstances are good, delayed LC can be considered to reduce the inconvenience of patients with a long-term catheter as much as possible.