Comparative analysis of the image quality and diagnostic performance of the zooming technique with diffusion-weighted imaging using different b-values for thyroid papillary carcinomas and benign nodules.

Objective: To compare image quality and diagnostic performance using different b-values for the zooming technique with diffusion-weighted imaging (ZOOMit-DWI) in thyroid nodules. Materials and methods: A total of 51 benign thyroid nodules and 50 thyroid papillary carcinomas were included. ZOOMit-DWI was performed with b-values of 0, 500, 1000, 1500 and 2000 s/mm2. The sharpness was evaluated as subjective index. The signal intensity ratio (SIR), signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) were measured as objective indices. Pairwise comparisons were performed among the different b-value groups using the Friedman test. A receiver operating characteristic curve of the ADC value was used to evaluate diagnostic performance. The DeLong test was used to compare diagnostic effectiveness among the different b-value groups. Results: In both the papillary carcinoma group (P = 0.670) and the benign nodule group (P = 0.185), the sharpness of nodules was similar between b-values of 1000 s/mm2and 1500 s/mm2. In the papillary carcinoma group, the SIRnodule was statistically higher in DWI images with a b-value of 1500 s/mm2than in DWI images with b-values of 500 s/mm2(P = 0.004), 1000 s/mm2(P = 0.002), and 2000 s/mm2(P = 0.003). When the b-values were 1500 s/mm2(P = 0.008) and 2000 s/mm2(P = 0.009), the SIRnodule significantly differed between the papillary carcinoma group and the benign nodule group. When b = 500 s/mm2, the ADC had an AUC of 0.888. When b = 1000 s/mm2, the ADC had an AUC of 0.881. When b = 1500 s/mm2, the ADC had an AUC of 0.896. When b = 2000 s/mm2, the ADC had an AUC of 0.871. The DeLong test showed comparable diagnostic effectiveness among the different b-value groups except for between b-values of 2000 s/mm2and 1500 s/mm2, with a b-value of 2000 s/mm2showing lower effectiveness. Conclusion: This study suggests that 1500 s/mm2may be a suitable b-value to differentiate benign and malignant thyroid nodules in ZOOMit-DWI images, which yielded better image quality.

Single-cell proteomics by mass spectrometry: Advances and implications in cancer research.

Cancer harbours extensive proteomic heterogeneity. Inspired by the prior success of single-cell RNA sequencing (scRNA-seq) in characterizing minute transcriptomics heterogeneity in cancer, researchers are now actively searching for information regarding the proteomics counterpart. Therefore recently, single-cell proteomics by mass spectrometry (SCP) has rapidly developed into state-of-the-art technology to cater the need. This review aims to summarize application of SCP in cancer research, while revealing current development progress of SCP technology. The review also aims to contribute ideas into research gaps and future directions, ultimately promoting the application of SCP in cancer research.

Crown ether decorated silicon photonics for safeguarding against lead poisoning.

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

Differential diagnosis of thyroid nodules by DCE-MRI based on compressed sensing volumetric interpolated breath-hold examination: A feasibility study.

OBJECTIVES: To explore the potential and performance of quantitative and semi-quantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on compressed sensing volumetric interpolated breath-hold (CS-VIBE) examination in the differential diagnosis of thyroid nodules. MATERIALS AND METHODS: A total of 208 patients with 259 thyroid nodules scheduled for surgery operation were prospectively recruited. All participants underwent routine and DCE-MRI. DCE-MRI quantitative parameters [Ktrans, Kep, Ve], semi-quantitative parameters [wash-in, wash-out, time to peak (TTP), arrival time (AT), peak enhancement intensity (PEI), and initial area under curve in 60 s (iAUC)] and time-intensity curve (TIC) types were analyzed. Differential diagnostic performances were assessed using area under the receiver operating characteristic curve (AUC) and compared with the Delong test. RESULTS: Ktrans, Kep, Ve, wash-in, wash-out, PEI and iAUC were statistically significantly different between malignant and benign nodules (P < 0.001). Among these parameters, ROC analysis revealed that Ktrans showed the highest diagnostic performance in the differentiation of benign and malignant nodules, followed by wash-in. ROC analysis also revealed that Ktrans achieved the best diagnostic performance for distinguishing papillary thyroid carcinoma (PTC) from non-PTC, follicular adenoma (FA) from non-FA, nodular goiter (NG) from non-NG, with AUC values of 0.854, 0.895 and 0.609, respectively. Type III curve is frequently observed in benign thyroid nodules, accounting for 77.4% (82/106). While malignant nodules are more common in type II, accounting for 57.5% (88/153). CONCLUSION: Thyroid examination using CS-VIBE based DCE-MRI is a feasible, non-invasive method to identify benign and malignant thyroid nodules and pathological types.

Intermittent tourniquet compared to throughout tourniquet use during Total Knee Arthroplasty in patients with Body Mass Index of 30 or more: A retrospective cohort study.

Background: Tourniquet use during total knee arthroplasty (TKA) reduces bleeding which optimises bone-cement interface for prosthesis stability and improves surgical field visualisation. However, prolonged usage can lead to complications and poorer outcomes. Some surgeons advocate for intermittent tourniquet application. Limited literature exists for patients with high body mass index (BMI). This study aims to compare the outcomes of intermittent tourniquet (IT) to throughout tourniquet (TT) use among obese patients undergoing primary TKA for knee osteoarthritis. Methods: This was a retrospective cohort study. In the TT group, tourniquet was inflated from the beginning and released once the bone cement has hardened. In the IT group, tourniquet was inflated at the beginning, released after initial incision and haemostasis, then inflated again during cementation. Tourniquet was released once the bone cement had set. Categorical outcome measures were analysed using Chi-squared or Fisher's exact test. T-test or Kruskal-Wallis test were used for continuous data. Results: When comparing IT to TT among patients with BMI≥30 (IT n = 48, TT n = 47), the mean duration of surgery was shorter in the TT group (p < 0.05). The difference in haemoglobin drop between the two groups was not statistically significant from post-operative day three onwards. There was no difference in transfusion rate (p > 0.05). ROM was greater in the IT group up to three weeks post-operatively (p < 0.05). When comparing patients with BMI <30 (n = 71) and BMI≥30 (n = 48) with IT use, there was no statistically significant difference in ROM and LOS. Conclusion: Patients with BMI≥30 in the IT group had greater ROM in the initial post-operative period. Although operative time and blood loss were greater among the IT group, there was no difference in transfusion rate. Outcomes of TKA performed with IT were similar for patients with BMI≥30 and BMI <30. The authors recommend intermittent tourniquet use during TKA for patients with BMI≥30. Level of evidence: 3.

Differential expression of follicular fluid exosomal microRNA in women with diminished ovarian reserve.

PURPOSE: Decreased ovarian reserve function is mainly characterized by female endocrine disorders and fertility decline. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been shown to regulate the function of granulosa cells (GCs). The present study explored differentially expressed miRNAs (DEmiRNAs) in patients with diminished ovarian reserve (DOR). METHODS: FF was collected from 12 DOR patients and 12 healthy controls. DEmiRNAs between the two groups were identified and analyzed using high-throughput sequencing technology and validated by real-time quantitative PCR (RT-qPCR). RESULTS: A total of 592 DEmiRNAs were identified using high-throughput miRNA sequencing, of which 213 were significantly upregulated and 379 were significantly downregulated. The sequencing results were further validated by RT-qPCR. These DEmiRNA target genes were mainly involved in the cancer pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, regulation of actin cytoskeleton signaling pathway, and biological processes related to protein binding, nucleoplasm, cytoplasm, and cell membrane. CONCLUSION: FF exosomal miRNAs are significantly differentially expressed in DOR patients versus non-DOR patients, underscoring their crucial role in regulating the pathogenesis of DOR.

Uncovering brain functional connectivity disruption patterns of lung cancer-related pain.

Pain is a pervasive symptom in lung cancer patients during the onset of the disease. This study aims to investigate the connectivity disruption patterns of the whole-brain functional network in lung cancer patients with cancer pain (CP+). We constructed individual whole-brain, region of interest (ROI)-level functional connectivity (FC) networks for 50 CP+ patients, 34 lung cancer patients without pain-related complaints (CP-), and 31 matched healthy controls (HC). Then, a ROI-based FC analysis was used to determine the disruptions of FC among the three groups. The relationships between aberrant FCs and clinical parameters were also characterized. The ROI-based FC analysis demonstrated that hypo-connectivity was present both in CP+ and CP- patients compared to HC, which were particularly clustered in the somatomotor and ventral attention, frontoparietal control, and default mode modules. Notably, compared to CP- patients, CP+ patients had hyper-connectivity in several brain regions mainly distributed in the somatomotor and visual modules, suggesting these abnormal FC patterns may be significant for cancer pain. Moreover, CP+ patients also showed increased intramodular and intermodular connectivity strength of the functional network, which could be replicated in cancer stage IV and lung adenocarcinoma. Finally, abnormal FCs within the prefrontal cortex and somatomotor cortex were positively correlated with pain intensity and pain duration, respectively. These findings suggested that lung cancer patients with cancer pain had disrupted connectivity in the intrinsic brain functional network, which may be the underlying neuroimaging mechanisms.

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.

Altered gray matter volume and functional connectivity in lung cancer patients with bone metastasis pain.

Bone metastasis pain (BMP) is a severe chronic pain condition. Our previous studies on BMP revealed functional brain abnormalities. However, the potential effect of BMP on brain structure and function, especially gray matter volume (GMV) and related functional networks, have not yet been clearly illustrated. Voxel-based morphometry and functional connectivity (FC) analysis methods were used to investigate GMV and intrinsic FC differences in 45 right-handed lung cancer patients with BMP(+), 37 lung cancer patients without BMP(-), and 45 healthy controls (HCs). Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Compared to HCs, BMP(+) group exhibited decreased GMV in medial frontal gyrus (MFG) and right middle temporal gyrus (MTG). Compared with BMP(-) group, BMP(+) group exhibited reduced GMV in cerebelum_6_L and left lingual gyrus. However, no regions with significant GMV differences were found between BMP(-) and HCs groups. Receiver operating characteristic analysis indicated the potential classification power of these aberrant regions. Correlation analysis revealed that GMV in the right MTG was positively associated with anxiety in BMP(+) group. Further FC analysis demonstrated enhanced interactions between MFG/right MTG and cerebellum in BMP(+) patients compared with HCs. These results showed that BMP was closely associated with cerebral alterations, which may induce the impairment of pain moderation circuit, deficits in cognitive function, dysfunction of emotional control, and sensorimotor processing. These findings may provide a fresh perspective and further neuroimaging evidence for the possible mechanisms of BMP. Furthermore, the role of the cerebellum in pain processing needs to be further investigated.

Longitudinal trajectory of amplitude of low-frequency fluctuation changes in breast cancer patients during neoadjuvant chemotherapy-A preliminary prospective study.

There is growing evidence that the amplitude of low-frequency fluctuation (ALFF) changes in breast cancer patients after chemotherapy. However, longitudinal changes in ALFF during chemotherapy are unclear. To assess the trajectory of ALFF changes during chemotherapy, 36 breast cancer patients underwent both resting-state functional magnetic resonance imaging and neuropsychological testing at three time points, including before neoadjuvant chemotherapy (NAC) (time point 0, TP0), after one cycle of NAC (before the second cycle of NAC, TP1), and upon completion of NAC (pre-operation, TP2). Healthy controls (HC) received the same assessments at matching time points. We compared the longitudinal changes of ALFF in the NAC and two HC groups. In the NAC group, compared with TP0, ALFF values in the right orbital part of the inferior frontal gyrus, left medial orbital part of the superior frontal gyrus, right insula, left medial part of the superior frontal gyrus, and right middle frontal gyrus declined significantly at TP1 and TP2. Compared with TP1, there were no significant changes in ALFF values at TP2. In the two HC groups, there were no significant changes in ALFF at corresponding intervals. We concluded that for breast cancer patients receiving NAC, ALFF values declined significantly in some brain regions after one cycle of NAC and then remained stable until the completion of NAC, and most of the brain regions with ALFF changes were located in the frontal lobe.

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease.

The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point-of-care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high-resolution mass spectrometry-based quantitative proteomics technology. We identified 19 upregulated (fold change = 1.5-5.8) and 51 downregulated proteins (fold change = 0.1-0.6) in the saliva samples of HFMD patients in comparison to that of healthy volunteers. Four upregulated protein candidates were selected for dot blot-based validation assay, based on novelty as biomarkers and exclusions in oral diseases and cancers. Salivary legumain was validated in the Singapore (n = 43 healthy, 28 HFMD cases) and Taiwan (n = 60 healthy, 47 HFMD cases) cohorts with an area under the receiver operating characteristic curve of 0.7583 and 0.8028, respectively. This study demonstrates the feasibility of a broad-spectrum HFMD POC diagnostic test based on legumain, a virus-specific host systemic signature, in saliva.

Suspensory Device Fixation of Lisfranc Injuries in a Southeast Asian Urban Population: Patient-Reported Functional Outcomes.

Introduction Open reduction internal fixation (ORIF) and primary arthrodesis are two conventional options for the treatment of Lisfranc injuries. However, they are associated with implant-related complications. An alternative suspensory device construct using interosseous nonabsorbable sutures with endobuttons has been described with satisfactory results. This study aims to explore functional outcomes after suture button fixation of Lisfranc injuries in a Southeast Asian population. Methods This was a single-surgeon retrospective study of patients with Lisfranc injuries treated surgically using a suture button fixation technique between 2017 and 2019. Data collected included demographic information, pre-injury levels of activity, nature of injury, and type of surgery performed. The minimum postoperative follow-up was one year. The Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM) were used to evaluate patient-reported outcomes. Scores were reported in percentage (%) with median and interquartile range. Results Twenty-nine patients with a mean age of 29 years (21-76) were recruited. Sixteen underwent suture button fixation only (SB), and 13 underwent suture button fixation with intercuneiform screw fixation and plating (SBM). The median scores for the FAOS and FAAM questionnaires were at least 80% in all domains. Twenty-eight patients (97%) were able to return to pre-injury activity level, 27 patients (93%) were able to return to sports. Only one patient was not satisfied with the outcomes of surgery. No patients had post-traumatic arthritis or hardware failure necessitating implant removal at the final follow-up. Conclusion This study has demonstrated that treatment of Lisfranc injuries with a suspensory device construct resulted in good outcomes with 97% of patients being able to return to pre-injury activity levels, and 93% of patients being able to return to sports. It may not be necessary to perform primary arthrodesis in uncomplicated Lisfranc injuries. This technique is also advantageous as implant removal is not routinely required due to the design and biomechanical properties of suspensory devices.

The Network Pharmacology Analysis of Tonifying Yang Formula for the Treatment of Diminished Ovarian Reserve.

Background: Diminished ovarian reserve (DOR) can lead to amenorrhea, infertility, and even the development of premature ovarian insufficiency, severely affecting the quality of life for women. Therefore, it is important to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential mechanisms of action. Objective: The study is aim to determine the main components of Tonifying Yang Formula, analyze the active substances and effective targets for treating DOR using Tonifying Yang Formula, and explore its potential molecular mechanisms of action, providing important theoretical basis for clinical application. Methods: The main active components of Tonifying Yang Formula and their potential therapeutic targets for DOR were searched using the Chinese Medicine Systems Pharmacology Database and Analysis Platform, BATMAN-TCM, GeneCards, OMIM, and Uniprot databases. The protein-protein interaction network of shared targets between drugs and diseases was constructed using the STRING database. The shared targets of drugs and diseases were subjected to GO analysis and KEGG pathway enrichment analysis using the DAVID database. AutoDock Vina was used to perform molecular docking between the active substances and key targets of the drug to validate their interaction activities. Results: The key chemical components in the Tonifying Yang Formula for DOR treatment include quercetin, luteolin, beta-sitosterol, stigmasterol, and kaempferol. The 164 key targets for treating DOR with Tonifying Yang Formula included AKT1, TNF, JUN, TP53, IL6, IL1B, EGFR, VEGFA, INS, and CASP3, among others. GO enrichment analysis revealed that the Tonifying Yang Formula mainly regulates gene expression positively, negatively regulates the apoptotic process, and affects signal transduction. KEGG pathway enrichment analysis showed that Tonifying Yang Formula is mainly involved in cancer-related pathways, the AGE-RAGE signaling pathway in diabetic complications, prostate cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. Molecular docking results indicated that the core components of the Tonifying Yang Formula had higher docking energies and stable binding with targets such as AKT1, IL6, JUN, TNF, and TP53. This study selected the PI3K/AKT signaling pathway for validation. Through experimental research, we found that Tonifying Yang Formula could improve ovarian reserve function by activating the PI3K/AKT signaling pathway. Conclusions: The potential mechanism of Tonifying Yang Formula therapy for DOR may be related to the influence of Chinese herbal compounds on pathways such as AKT1, IL6, JUN, TNF, and TP53, regulating the proliferation and apoptosis of ovarian granulosa cells, maintaining the function of the ovarian corpus luteum, regulating the secretion of related hormones, and alleviating ovarian tissue inflammation.

Synergistic Effects in Bimetallic (Co, Mn)-Doped SnO2 Nanobelts for Greatly Enhanced Gas-Sensing Properties.

Enhanced physical and chemical properties of materials through bimetallic synergistic effects remain a challenging problem because it is difficult to construct well-defined bimetallic synergies. Here, a series of bimetallic (Co, Mn)-codoped SnO2 nanobelts were synthesized through the chemical vapor deposition (CVD) method by precisely controlling Co and Mn contents. The results show that the interaction between Co and Mn sites not only affects the chemical coordination environment of SnO2 nanobelts and promotes the activity of an electronic catalytic reduction reaction but also greatly improves the gas-sensing properties. At the working temperature of 300 °C, the response value of the gas sensor to 200 ppm ethanol reaches an amazing 311.9. The amount of oxygen adsorbed on the surface of the sensitive material plays a crucial role in the gas-sensing response of the material. X-ray photoelectron spectroscopic analysis (XPS) spectra of the O 1s region of the sensor show that the adsorption oxygen content is 37.96%, which is higher than that of pure SnO2 (27.41%). The increase of adsorbed oxygen content can be attributed to the synergistic effect of Co and Mn bimetal, which leads to electron enrichment on the surface of SnO2 and promotes the activation of SnO2, and helps to improve the gas-sensitive characteristics of SnO2.

Insights into DNMT1 and programmed cell death in diseases.

DNMT1 (DNA methyltransferase 1) is the predominant member of the DNMT family and the most abundant DNMT in various cell types. It functions as a maintenance DNMT and is involved in various diseases, including cancer and nervous system diseases. Programmed cell death (PCD) is a fundamental mechanism that regulates cell proliferation and maintains the development and homeostasis of multicellular organisms. DNMT1 plays a regulatory role in various types of PCD, including apoptosis, autophagy, necroptosis, ferroptosis, and others. DNMT1 is closely associated with the development of various diseases by regulating key genes and pathways involved in PCD, including caspase 3/7 activities in apoptosis, Beclin 1, LC3, and some autophagy-related proteins in autophagy, glutathione peroxidase 4 (GPX4) and nuclear receptor coactivator 4 (NCOA4) in ferroptosis, and receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like protein (RIPK1-RIPK3-MLKL) in necroptosis. Our study summarizes the regulatory relationship between DNMT1 and different types of PCD in various diseases and discusses the potential of DNMT1 as a common regulatory hub in multiple types of PCD, offering a perspective for therapeutic approaches in disease.

Single-cell sequencing provides insights into the landscape of ovary in PCOS and alterations induced by CUMS.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder related to psychological distress. However, the mechanism underlying increased prevalence of depression in PCOS remained unclear. This study aimed to explore the unique transcriptional landscape of ovary and offered a platform to explore the mechanism of PCOS, as well as the influences caused by depression. The PCOS rat model was established by letrozole whereas PCOS rat model with depression was established by letrozole combined with chronic unpredicted mild stress (CUMS). Then single-cell RNA sequencing (scRNA-Seq) was applied to analyze the transcriptional features of rat ovaries. Granulosa cells (GCs) and fibroblasts (Fibros) accounted for the top two clusters of total 12 cell types. There were nine clusters in GCs, related to inflammatory response, endoplasmic reticulum (ER) stress, and steroidogenesis. The expression of differentially expressed genes (DEG) Hes1 was higher in PCOS and PCOS + CUMS groups, exhibiting enhanced expression by pseudotime and positively related to inflammation. Pseudotemporal analysis revealed that inflammation contributed to the different GCs distributions. Moreover, analysis of DEGs and gene ontology (GO) function enrichment revealed CUMS aggravated inflammation in PCOS GCs possibly via interferon signaling pathway. In theca cells (TCs), nine clusters were observed and some of them were relevant to inflammation, ER stress, and lipid metabolism. DEGs Ass1, Insl3, and Ifi27 were positively related to Cyp17a1, and Ces1d might contribute to the different trajectory of TCs. Subsequent scRNA-seq revealed a signature profile of endothelial cells (ECs) and Fibros, which suggest that inflammation-induced damage of ECs and Fibro, further exacerbated by CUMS. Finally, analysis of T cells and mononuclear phagocytes (MPs) revealed the existence of immune dysfunction, among which interferon signaling played a critical role. These findings provided more knowledge for a better understanding PCOS from the view of inflammation and identified new biomarkers and targets for the treatment of PCOS with psychological diseases.NEW & NOTEWORTHY In this study, we mapped the landscape of polycystic ovary syndrome (PCOS) ovary with rat model induced by letrozole and provided a novel insight into the molecular mechanism of PCOS accompanied by chronic unpredicted mild stress (CUMS) at single-cell transcriptomic level. These observations highlight the importance of inflammation in the pathogenesis of PCOS, which might also be the bridge between PCOS and psychological diseases.

Protocatechuic acid alleviates polycystic ovary syndrome symptoms in mice by PI3K signaling in granulosa cells to relieve ROS pressure and apoptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated gynecological endocrine disease that occurs in women of childbearing age. Protocatechuic acid is a phenol-rich compound derived from herbs and owns vital functions in numerous diseases. Howbeit, protocatechuic acid's impact on PCOS is unknown. METHODS: A combination of in vivo and in vitro models was examined in this study. C57BL/6 mice were injected subcutaneously daily with dehydroepiandrosterone to establish a PCOS mouse model, and protocatechuic acid was intraperitoneally injected into PCOS mice. Granulosa cells of PCOS ovaries were also isolated. The function of protocatechuic acid was appraised using enzyme-linked immunosorbent assay, hematoxylin-eosin staining, reactive oxygen species (ROS) and LC3 levels analysis, flow cytometry, quantitative real-time PCR, and western blot. Meanwhile, the mechanism of protocatechuic acid was assessed with a series of molecular experiments. RESULTS: Protocatechuic acid owned no apparent toxic effect on mice. Functionally, protocatechuic acid owned a function of mitigating PCOS in vivo. Meanwhile, protocatechuic acid repressed ROS, autophagy, and apoptosis of PCOS ovarian granulosa cells in vitro. Mechanistically, rescue assays elucidated that the protective function of protocatechuic acid against PCOS was interrelated to the activation of the PI3K/AKT/mTOR axis. CONCLUSION: Protocatechuic acid alleviated PCOS symptoms in mice through PI3K signaling in granulosa cells to reduce ROS levels and apoptosis.

Breaking the Barrier: A Study on Multi-drug Resistance in Breast Abscess at an Academic Malaysian Hospital.

BACKGROUND: In recent years, the increase in antibiotics usage locally has led to a worrying emergence of multi-drug resistant organisms (MDRO), with the Malaysian prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) ranging from 17.2 to 28.1% between 1999 and 2017. A study has shown that 7% of all non-lactational breast abscesses are caused by MRSA. Although aspiration offers less morbidities compared to surgical drainage, about 20% of women infected by MRSA who initially underwent aspiration subsequently require surgical drainage. This study is conducted to determine the link between aetiology, antimicrobial resistance pattern and treatment modalities of breast abscesses. METHODS: Retrospective study of reviewing microbiology specimens of breast abscess patients treated at Universiti Malaya Medical Centre from 2015 to 2020. Data collected from microbiology database and electronic medical records were analysed using SPSS V21. RESULT: A total of 210 specimens from 153 patients were analysed. One-fifth (19.5%) of the specimens isolated were MDRO. Lactational associated infections had the largest proportion of MDR in comparison to non-lactational and secondary infections (38.5%, 21.7%, 25.7%, respectively; p = 0.23). Staphylococcus epidermidis recorded the highest number of MDR (n = 12) followed by S. aureus (n = 8). Adjusted by aetiological groups, the presence of MDRO is linked to failure of single aspirations (p = 0.554) and significantly doubled the risk of undergoing surgical drainage for resolution (p = 0.041). CONCLUSION: MDR in breast abscess should be recognised as an increasing healthcare burden due to a paradigm shift of MDRO and a rise of resistance cases among lactational associated infection that were vulnerable to undergo surgical incision and drainage for resolution.

Efficiency of Chinese medicine Bushen Huatan formula for treatment of polycystic ovary syndrome in mice via regulating gut microbiota and PPARγ pathway. / è¡¥è‚¾åŒ–ç—°æ–¹é€šè¿‡è°ƒæŽ§è‚ é“èŒåŠPPARγ通路治疗多囊卵巢综合征的机制.

OBJECTIVES: To explore the effect and mechanism of Chinese medicine Bushen Huatan formula in treatment of polycystic ovary syndrome (PCOS). METHODS: Twenty-four SPF female C57BL/6J mice were randomly divided into 3 groups with 8 animals in each group. Control group was given drinking water ad libitum; PCOS was induced by giving letrozole gavage and high-fat diet in model group and treatment group; treatment group received Bushen Huatan formula suspension for 35 d. The sex hormone levels of mice were detected by enzyme-linked immunosorbent assay. Ovary morphology was observed under light microscope after hematoxylin and eosin staining. The feces in the colon of mice were collected, and the gut microbiota was detected by 16S rRNA sequencing. The short chain fatty acids were detected by gas chromatography-mas spectrometry. The expression of peroxisome proliferator activated receptor (PPARγ) was detected by immunohistochemistry. The mRNA expression of mucin-2, occludin-1, tight junction protein zonula occludens 1 (ZO-1) and PPARγ in intestinal epithelium were detected by realtime RT-PCR. The expression of inducible nitric oxide synthase (iNOS) and PPARγ was detected by Western blotting. RESULTS: Compared with the control group, the body weight, serum levels of follicle stimulating hormone, luteinizing hormone and testosterone in the model group were increased, and serum levels of estradiol were decreased (all P<0.01); the ovarian structure under light microscope was consistent with the characteristics of PCOS. Compared with the model group, the serum levels of sex hormone and ovarian structure in treatment group were improved. The overall structure of gut microbiota in PCOS model mice changed. Compared with control group, there were significantly reduced abundance of Firmicutes, and increased abundance of Verrucomicrobia, Proteobacteria and Actinobacteria inthe model group at phylum level (all P<0.05); there were significantly reduced abundance of Lactobacillus, and increased abundance of Akkermansia, Lachnoclostridium, Lactococcus and Eubacterium_coprostanoligenes at genus level (all P<0.05). The disordered condition of gut microbiota was significantly improved in treatment group. Compared with control group, the contents of acetic acid, propionic acid and butyric acid in feces of model group were significantly decreased (all P<0.05); while the contents of propionic acid and butyric acid in treatment group were significantly increased compared with model control group (both P<0.05). Compared with control group, the mRNA expression of ZO-1 and protein expression of iNOS in model group were significantly increased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were significantly decreased (all P<0.05). Compared with model group, the mRNA expression of ZO-1 and protein expression of iNOS in treatment group were decreased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were increased. CONCLUSIONS: PCOS induced by letrozole high-fat diet induces microflora imbalance in mice. Chinese medicine Bushen Huatan formula may increase the level of short chain fatty acid by regulating gut microbiota, thereby activating the intestinal PPARγ pathway and improving intestinal barrier function to act as a cure for PCOS.

Targeting pyroptosis as a preventive and therapeutic approach for stroke.

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1ß before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke. The role of pyroptosis after stroke. After stroke, microglia first rush to the damaged area and polarize into M1 and M2 types. Under the influence of various stimuli, microglia undergo pyroptosis, release pro-inflammatory factors, and are converted to the M1 type; astrocytes and neuronal cells also undergo pyroptosis under the stimulation of various pro-inflammatory factors, leading to astrocyte death due to increased osmotic pressure in the membrane, resulting in water absorption and swelling until rupture. BMECs, the main structural component of the BBB, also undergo pyroptosis when stimulated by pro-inflammatory factors released from microglia and astrocytes, leading to the destruction of the structural integrity of the BBB, ultimately causing more severe brain damage. In addition, GSDMD in neutrophils mainly mediate the release of NETs rather than pyroptosis, which also aggravates brain injury. IL-10=interleukin-10; TGF-ß = transforming growth factor-ß; IL-18=interleukin-18; IL-1ß = interleukin-1ß; TNF-α = tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; GSDMD = gasdermin D; BMECs=brain microvascular endothelial cells; BBB = blood-brain barrier.