Outcomes after fertility-sparing surgery of early-stage ovarian cancer: A nationwide population-based study.

BACKGROUND: Fertility-sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early-stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. METHODS: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early-stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site-specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier method with log-rank test and Cox regression model. RESULTS: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high-grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66-1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06-0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. CONCLUSION: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS.

Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator 7 (NCOA7) both preserved lysosomal acidification and served as a homeostatic brake to constrain EC immunoactivation. Conversely, NCOA7 deficiency promoted lysosomal dysfunction and proinflammatory oxysterol/bile acid generation that, in turn, contributed to EC pathophenotypes. In vivo, mice deficient for Ncoa7 or exposed to the inflammatory bile acid 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) displayed worsened PAH. Emphasizing this mechanism in human PAH, an unbiased, metabolome-wide association study (N=2,756) identified a plasma signature of the same NCOA7-dependent oxysterols/bile acids associated with PAH mortality (P<1.1x10-6). Supporting a genetic predisposition to NCOA7 deficiency, in genome-edited, stem cell-derived ECs, the common variant intronic SNP rs11154337 in NCOA7 regulated NCOA7 expression, lysosomal activity, oxysterol/bile acid production, and EC immunoactivation. Correspondingly, SNP rs11154337 was associated with PAH severity via six-minute walk distance and mortality in discovery (N=93, P=0.0250; HR=0.44, 95% CI [0.21-0.90]) and validation (N=630, P=2x10-4; HR=0.49, 95% CI [0.34-0.71]) cohorts. Finally, utilizing computational modeling of small molecule binding to NCOA7, we predicted and synthesized a novel activator of NCOA7 that prevented EC immunoactivation and reversed indices of rodent PAH. In summary, we have established a genetic and metabolic paradigm and a novel therapeutic agent that links lysosomal biology as well as oxysterol and bile acid processes to EC inflammation and PAH pathobiology. This paradigm carries broad implications for diagnostic and therapeutic development in PAH and in other conditions dependent upon acquired and innate immune regulation of vascular disease.

MOF@COF Nanocapsules Enhance Soft Tissue Sarcoma Treatment: Synergistic Effects of Photodynamic Therapy and PARP Inhibition on Tumor Growth Suppression and Immune Response Activation.

Soft tissue sarcomas (STS) are highly malignant tumors with limited treatment options owing to their heterogeneity and resistance to conventional therapies. Photodynamic therapy (PDT) and poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown potential for STS treatment, with PDT being effective for sarcomas located on the extremities and body surface and PARPi targeting defects in homologous recombination repair. To address the limitations of PDT and harness the potential of PARPi, herein, a novel therapeutic approach for STS treatment combining nanocapsules bearing integrated metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), i.e., MOF@COF, with PDT and PARPi is proposed. Nanocapsules are designed, referred to as ZTN@COF@poloxamer, which contain a Zr-based MOF and tetrakis (4-carbethoxyphenyl) porphyrin as a photosensitizer, are coated with a COF to improve the sensitizing properties, and are loaded with niraparib to inhibit DNA repair. Experiments demonstrate that this new nanocapsules treatment significantly inhibits STS growth, promotes tumor cell apoptosis, exhibits high antitumor activity with minimal side effects, activates the immune response of the tumor, and inhibits lung metastasis in vivo. Therefore, MOF@COF nanocapsules combined with PARPi offer a promising approach for STS treatment, with the potential to enhance the efficacy of PDT and prevent tumor recurrence.

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates.

BACKGROUND: Large-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. METHODS: We conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. RESULTS: Among 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. CONCLUSIONS: Plasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.

Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11ß1 on Fibroblasts to Form a Lung Metastatic Niche.

Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer.

Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM. IMPLICATIONS: SB9 as a therapeutic target for LCBM.

Computer-Vision Based Gesture-Metasurface Interaction System for Beam Manipulation and Wireless Communication.

Hand gesture plays an important role in many circumstances, which is one of the most common interactive methods in daily life, especially for disabled people. Human-machine interaction is another popular research topic to realize direct and efficient control, making machines intelligent and maneuverable. Here, a special human-machine interaction system is proposed and namedas computer-vision (CV) based gesture-metasurface interaction (GMI) system, which can be used for both direct beam manipulations and real-time wireless communications. The GMI system first needs to select its working mode according to the gesture command to determine whether to perform beam manipulations or wireless communications, and then validate the permission for further operation by recognizing unlocking gesture to ensure security. Both beam manipulation and wireless communication functions are validated experimentally, which show that the GMI system can not only realize real-time switching and remote control of different beams through gesture command, but also communicate with a remote computer in real time by translating the gesture language to text message. The proposed non-contact GMI system has the advantages of good interactivity, high flexibility, and multiple functions, which can find potential applications in community security, gesture-command smart home, barrier-free communications, and so on.

ZNF70 regulates IL-1ß secretion of macrophages to promote the proliferation of HCT116 cells via activation of NLRP3 inflammasome and STAT3 pathway in colitis-associated colorectal cancer.

Chronic inflammation is a key driver for colitis-associated colorectal cancer (CAC). It has been reported that inflammatory cytokines, such as IL-1ß, could promote CAC. Zinc finger protein 70 (ZNF70) is involved in multiple biological processes. Here, we identified a previously unknown role for ZNF70 regulates macrophages IL-1ß secretion to promote HCT116 proliferation in CAC, and investigated its underlying mechanism. We showed ZNF70 is much higher expressed in CAC tumor tissues compared with adjacent normal tissues in clinical CAC samples. Further experiments showed ZNF70 promoted macrophages IL-1ß secretion and HCT116 proliferation. In LPS/ATP-stimulated THP-1 cells, we found ZNF70 activated NLRP3 inflammasome, resulting in robust IL-1ß secretion. Interestingly, we discovered the ZnF domain of ZNF70 could interact with NLRP3 and decrease the K48-linked ubiquitination of NLRP3. Moreover, ZNF70 could activate STAT3, thereby promoting IL-1ß synthesis. Noteworthy, ZNF70 enhanced proliferation by upregulating STAT3 activation in HCT116 cells cultured in the conditioned medium of THP-1 macrophages treated with LPS/ATP. Finally, the vivo observations were confirmed using AAV-mediated ZNF70 knockdown, which improved colitis-associated colorectal cancer in the AOM/DSS model. The correlation between ZNF70 expression and overall survival/IL-1ß expression in colorectal cancer was verified by TCGA database. Taken together, ZNF70 regulates macrophages IL-1ß secretion to promote the HCT116 cells proliferation via activation of NLRP3 inflammasome and STAT3 pathway, suggesting that ZNF70 may be a promising preventive target for treating in CAC.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

Advanced maternal age-related clustering of metabolic abnormalities is associated with risks of adverse pregnancy outcomes.

AIMS: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes. METHOD: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m2, plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg. RESULT: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age. CONCLUSION: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes.

Wearable Transmitter Coil Design for Inductive Wireless Power Transfer to Implantable Devices.

Wireless endovascular sensors and stimulators are emerging biomedical technologies for applications such as endovascular pressure monitoring, hyperthermia, and neural stimulations. Recently, coil-shaped stents have been proposed for inductive power transfer to endovascular devices using the stent as a receiver. However, less work has been done on the external transmitter components, so the maximum power transferable remains unknown. In this work, we design and evaluate a wearable transmitter coil that allows 50 mW power transfer in simulation.Clinical Relevance-This allows more accurate measurements and precise control of endovascular devices.

Risk of placenta accreta spectrum following myomectomy: a nationwide cohort study.

BACKGROUND: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. OBJECTIVE: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. STUDY DESIGN: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. RESULTS: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. CONCLUSION: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer.

Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

Prognostic nutritional index and neutrophil-lymphocyte ratio predict toxicities and prognosis in patients with cervical cancer treated with curative radiochemotherapy.

BACKGROUND: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. METHODS: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. RESULTS: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (<49.5) or high NLR (>2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. CONCLUSIONS: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Nontuberculous mycobacterial infection mimicking gynecologic malignancy in a woman living with HIV.

The weakened immune system in people living with HIV (PLWH) can lead to infectious diseases occurring more aggressively and mimicking the clinical manifestations of malignancies. Mycobacterium sherrisii, a slow-growing nontuberculous mycobacterium, may cause opportunistic infections among PLWH. We present a case of a 41-year-old woman who initially presented with fever, vaginal spotting, and a bulky pelvic mass, raising suspicion of uterine malignancy. Following a surgical resection, she was pathologically diagnosed with leiomyoma and endometriosis. However, during an event of needlestick injury, she was unexpectedly found to be HIV-infected and the CD4 count was 157 cells/µL at diagnosis, which prompted a diagnostic work-up for opportunistic infections. The diagnosis of disseminated M. sherrisii infection was confirmed through cultures and special staining of specimens obtained from the pelvic tumor and blood. Subsequently, she was treated with a combination of ethambutol, azithromycin, and levofloxacin. Two months after treatment, abdominal and pelvic computed tomography revealed no evidence of recurrent tumor or abscess formation. Given the frequent association of pelvic masses with gynecologic malignancies in women living with HIV, it can be challenging to differentiate between a cancerous lesion and an infectious process, emphasizing the need for meticulous investigations to minimize the potential for misdiagnosis.

The effect of exercise on the risk of metabolic syndrome associated with sleep insufficiency: a cross-sectional study.

Introduction: Sleep disturbance and insufficient sleep have been linked to metabolic syndrome, increasing cardiovascular disease and mortality risk. However, few studies investigate the joint effect of sleep and exercise on metabolic syndrome. We hypothesized that regular exercise can mitigate the exacerbation of metabolic syndrome by sleep insufficiency. Objective: The aim of this study was to investigate whether exercise can attenuate or eliminate the relationship between sleep insufficiency and metabolic syndrome. Method: A total of 6,289 adults (mean age = 33.96 years; women: 74.81%) were included in the study, a cross-sectional study conducted based on the results of employee health screening questionnaires and databases from a large healthcare system in central Taiwan. Participants reported sleep insufficiency or not. Self-reported exercise habits were classified into 3 levels: no exercise, exercise <150 min/week, and exercise ≧150 min/week. Multiple logistic regression and sensitivity analyses were conducted to understand the joint associations of sleep patterns and exercise with metabolic syndrome with exposure variables combining sleep duration/disturbances and PA. Results: Compared with the reference group (sufficient sleep), individuals with sleep insufficiency had a higher risk for metabolic syndrome [adjusted odds ratio (AOR) = 1.40, 95% confidence interval (95% CI): 1.01-1.94, p < 0.05] in females aged 40-64 years, but not in other populations. Sleep insufficiency was not associated with the risk of metabolic syndrome among individuals achieving an exercise level of <150 min/week, and in particular among those achieving ≧150 min/week in all populations in our study. Conclusion: Sleep insufficiency was related to a higher risk of metabolic syndrome in female healthcare staff aged 40-64 years. Being physically active with exercise habits in these individuals, the risk of metabolic syndrome was no longer significant.