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Abstract Background The contribution of interspecies interactions between coinfecting pathogens to chronic refractory infection by affecting pathogenicity is well established. However, little is known about the impact of intraspecific interactions on infection relapse, despite the cross-talk of different strains within one species is more common in clinical infection. We reported a case of chronic refractory pulmonary infection relapse, caused by two methicillin-sensitive S. aureus (MSSA) strains (SA01 and SA02) and revealed a novel strategy for relapse via intraspecific cooperation. Methods The hemolytic ability, growth curve, biofilm formation, virulence genes and response of G. mellonella larvae to S. aureus infection were analysed to confirm this hypothesis. Results SA02 hemolytic activity was inhibited by SA01, along with the expression of hemolysin genes and the virulence factor Hla. Additionally, SA01 significantly enhanced the biofilm formation of SA02. AIP-RNAIII may be a possible pathway for this interaction. Compared with mono-infection, a worse outcome (decreased larval survival and increased microbial burden) of the two MSSA strains coinfected with G. mellonella confirmed that intraspecific interactions indeed enhanced bacterial survival in vivo. Conclusion The intraspecific interaction of S. aureus could lead to chronic refractory infection via pathogenicity changes.

Abstract Background Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. Methods This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women’s and Children’s Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. Results Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p

Staphylococcus aureus (S. aureus) is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus, contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB. We constructed NCTC 8325 ∆glmS for further validation. qRT-PCR analysis revealed that AGEs promoted both glmS and sigB expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆glmS. NCTC 8325 ∆glmS showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆glmS. Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.

Objective: We aimed to determine the safety of Vaginal natural orifice transluminal endoscopic surgery (vNOTES) in terms of the Enhanced Recovery after Surgery (ERAS) concept for tubal pregnancy surgery and provide a detailed process of vNOTES for tubal pregnancy surgery, including experience and key points for surgeons performing this procedure. Methods: The Longitudinal Vaginal Natural Orifice Transluminal Endoscopic Surgery Study (LovNOTESS), which was conducted in Chengdu, China. A total of 219 patients who underwent tubal ectopic pregnancy surgery between September 2021 and March 2022. The patients underwent salpingectomy or salpingostomy using transumbilical laparoendoscopic single-site surgery (LESS) or vNOTES, according to their preferences. This study prospectively collected perioperative and one-year follow-up data on tubal pregnancy outcomes after vNOTES and compared them with those after LESS. Results: The vNOTES group showed a shorter surgical duration, hospitalization duration, and postoperative exhaust time and a lower analgesic medication usage rate, but it showed a higher surgical conversion rate. The vNOTES approach reduced the postoperative exhaust time by approximately 9 h (95% confidence interval [CI]: −11.93, −5.57 h, p

Despite the growing evidence that stressful life events are associated with adolescent non-suicidal self-injury (NSSI), few studies have investigated the mediating and moderating mechanisms underlying this link. The current study examined whether sleep quality mediated the link between stressful life events and NSSI and whether this mediating process was moderated by adolescent sensation seeking. The participants were 1006 Chinese adolescents (48.21% boys; mean age = 13.16 years, SD = 0.67). They completed the Life Events Checklist, Pittsburgh Sleep Quality Index, UPPS-P Impulsive Behavior Scale, and NSSI Questionnaire. The PROCESS macro for SPSS was used to examine the hypothesized moderated mediation model. The results showed that sleep quality significantly mediated the positive association between stressful life events and adolescent NSSI. Moreover, this mediating pathway was moderated by sensation seeking. Specifically, the risk impact of stressful life events on NSSI through sleep quality was significant only among adolescents with high-level sensation seeking but not among those with low-level sensation seeking. These findings provide intervention insights to reduce the risk of adolescent NSSI.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma are common subtypes of thyroid cancer, while hyalinizing trabecular tumor (HHT) of the thyroid is a rare peculiar type of follicular cell neoplasm. Although all three tumor types originate from thyroid follicular cells, the frequency of their co-presence in the same thyroid gland is unknown. Herein, we describe an extremely rare case with three types of concurrent thyroid neoplasms in one patient. This patient was a 60-year-old female who presented with large symptomatic multinodular goiter clinically. Fine needle aspiration of the right thyroid nodule showed atypia of undetermined significance. She then received total thyroidectomy. Microscopically, there were 3 types of tumors identified: multifocal (x4) PTC (largest focus 1.5 cm) with focal tall cell features, encapsulated angioinvasive oncocytic carcinoma (8.2 cm), and a small HHT (0.6 cm). The HHT was encapsulated, containing spindled to polygonal cells with oval to elongated nuclei arranged in a trabecular growth pattern. The PTC and oncocytic carcinoma were diagnosed by morphology only. The diagnosis of HHT was confirmed by immunohistochemistry showing the tumor cells to be positive for pan-cytokeratin, thyroglobulin, TTF-1, and PAX8, while negative for synaptophysin, chromogranin, and calcitonin. Next generation sequencing demonstrated different molecular alterations: BRAF V600E mutation in PTC; NRAS mutation in oncocytic carcinoma, and HRAS mutation in HHT. This is the first case report of triple thyroid neoplasms occurring synchronously in one patient. The unique genetic alteration of each individual tumor suggests different pathogenetic mechanisms.

Intrinsic capacity is central to the maintenance of function in older adults, and maintaining optimal intrinsic capacity is of great importance to promote healthy aging. The purpose of this systematic review and meta-analysis was to analyze the impact of multi-domain interventions on intrinsic capacity in older adults, intervention components, and potential interactions between components. A total of 6740 published articles were screened until August 2022, and the review included 25 randomized controlled trials that analyzed populations, interventions, control groups, and outcomes. The meta-analysis showed improvements in the primary outcome indicators in the intervention group compared to the control group. These included increased scores on the Mini-Mental State Examination as an indicator of cognitive function, decreased scores on the Geriatric Depression Scale (GDS-15) as an indicator of psychological ability and increased scores on the Short Physical Performance Battery (SPPB) as an indicator of physical performance, with only the SPPB indicator analyzed showing greater heterogeneity. Significant improvements were also seen in the secondary indicators Time-to-Walk Test (TUG), gait speed, Chair Stand Test (CST), grip strength values and BMI. There was insufficient data for the Mini Nutritional Assessment (MNA) as an indicator of vitality to conduct a meta-analysis. Studies were of moderate to high quality. The results of this review indicate that multi-domain interventions can maintain the level of intrinsic capacity in older adults and are equally effective in older adults with declining self-care abilities.

The fruits of leguminous plants Cercis Chinensis Bunge are still overlooked although they have been reported to be antioxidative because of the limited information on the phytochemicals of C. chinensis fruits. A simple, rapid and sensitive HPLC-MS/MS method was developed for the identification and quantitation of the major bioactive components in C. chinensis fruits. Eighteen polyphenols were identified, which are first reported in C. chinensis fruits. Moreover, ten components were simultaneously quantified. The validated quantitative method was proved to be sensitive, reproducible and accurate. Then, it was applied to analyze batches of C. chinensis fruits from different phytomorph and areas. The principal components analysis (PCA) realized visualization and reduction of data set dimension while the hierarchical cluster analysis (HCA) indicated that the content of phenolic acids or all ten components might be used to differentiate C. chinensis fruits of different phytomorph.

Abstract Background Congenital hepatic fibrosis (CHF) is a rare inherited form of ductal plate malformation associated with polycystic kidney disease. The diagnosis requires histopathologic confirmation, but can be challenging to distinguish from other undefined fibrocystic liver diseases. We aimed to describe the clinicopathologic features of congenital hepatic fibrosis (CHF), with comparisons to other entities that may clinically and/or histologically mimic CHF. Methods Nineteen cases that carried a clinical and/or histologic impression of CHF were identified at our institution, of which the histology was reassessed and reappraised into two categories: CHF (n=13) and mimics (n=6). The clinicopathologic features between the two groups were analyzed and compared. Results The CHF group was further sub-classified into those with clinical suspicion (CHF-c, n=8) and those as incidental histology findings (CHF-i, n=5). Patients of CHF-i were much older than CHF-c or mimics (P

The roots of O. fragrans are also a valuable resource in addition to its flowers and fruits. In this study, the HPLC-MS/MS method used for analyzing the chemical constituents in O. fragrans roots extract was developed, which showed high sensitivity for both qualitative and quantitative analyses. Thirty-two compounds were first discovered in O. fragrans roots, one compound of which was reported for the first time. The simultaneous determination method for acteoside, isoacteoside, oleuropein and phillyrin was validated to be sensitive and accurate. Then it was applied to determine the content of bioactive components in O. fragrans roots from different cultivars. The content of oleuropein and phillyrin in the twelve batches was relatively stable, while the content of acteoside and isoacteoside varied greatly. Moreover, the therapeutic material basis and mechanism of O. fragrans roots exerting its traditional pharmacodynamics were analyzed by network pharmacology. The results showed that O. fragrans roots might be effective for the treatment of inflammation, cardiovascular diseases, cancer, and rheumatoid arthritis, which is consistent with the traditional pharmacodynamics of O. fragrans roots. This work can provide an analytical method for the comprehensive development of O. fragrans roots.

Abstract Background Hepatic stellate cell (HSC) activation plays a pivotal role in hepatic inflammation and liver fibrosis. TLR4 pathway activation has been reported to be involved in mice liver fibrosis induced by hepatitis virus infection, alcohol abuse, biliary ligation, carbon tetrachloride 4 treatment, and Schistosoma japonicum (Sj) infection. The effect and mechanisms of the cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear. Methods Mice liver fibrosis were induced by cutaneous infection of Sj cercariae. COX-2 inhibitor, NS398 were injected from week 5 to week 7, while TLR4 inhibitor TAK242 were injected from week 4 to week 8 post Sj infection. Human HSCs line, LX-2 cells were cultured and exposed to LPS or synthetic PGE2, or pretreated by TAK242, TLR4-siRNA or NS398. Liver tissue and serum or in vitro cultured cell lysaste were collected at indicated time courses for exploring the relationship between TLR4 and COX2-PGE2 axis through qPCR, western blot, immunohistochemical assay, ect. One-way analysis of variance among multiple groups followed by Uncorrected Fisher’s LSD-t test or paired comparisons through t test were performed to tell the statistical differences. Results This study investigated the link between the COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culture of HSC strain-LX-2. The COX2/PGE2 axis was positively associated with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis in Sj-infected mice and in lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated cultured HSCs through upregulation of alpha smooth muscle actin (α-SMA) expression. In LPS-triggered HSCs, NS398, a COX2 inhibitor, led to suppression of PGE2 synthesis and reduced expression of α-SMA and type I collagen (COL I). Conclusions These results indicate firstly the positive association of the COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may at least partially control the COX2/PGE2 axis in Sj-infected mice liver and in vitro cultured HSCs. The COX2/PGE2-EP2/EP4 axis might be a good drug target against liver fibrosis induced by Sj infection. Graphic abstract

Abstract Background With increasing cancer incidence and decreasing cancer mortality, there is a growing need for a valid and culturally adapted tool to measure health-related quality of life in children with cancer. This study validated the DISABKIDS Chronic Generic Module (DCGM-37) in Chinese children and adolescents with cancer. Methods The DCGM-37 was translated and adapted for use in China following the guidelines from its copyright holders. In total, 140 children and adolescents with cancer and their guardians were included in this cross-sectional study. Internal consistency and test-retest reliability were evaluated. Convergent validity was examined using Pearson correlation between the DCGM-37 and the PedsQL 4.0 Generic Core Scale. Dimensionality was clarified using exploratory factor analysis. Discriminant validity was evaluated by comparing DCGM-37 scores by sex, age, family income, and clinical characteristics. Results Internal consistency (Cronbach’s alpha 0.91) and test–retest reliability were good (intraclass correlation coefficient 0.87, 95% confidence interval 0.73–0.94). Strong correlations between the DCGM-37 and the PedsQL 4.0 (r = 0.83) suggest good convergent validity. Six factors explained 51.94% of the total variance. Children with leukemia scored higher than those with sarcoma in all subscales (effect size ranged from 0.39 to 0.83), especially the “social exclusion” subscales (effect size 0.83). Small to moderate differences (effect size ranged from 0.38 to 0.58) were observed by sex, age, and family income. Neither floor nor ceiling effects were observed. Conclusion The DCGM-37 is reliable and valid for measuring health-related quality of life in Chinese children and adolescents with cancer.

Abstract Background Chinese government launched a pilot study on public long-term care insurance (LTCI) recently. Guangzhou is one of the fifteen pilot cities, officially started providing LTCI in August 2017. An in-depth analysis of experimental data from the pilot city may provide suggestions for developing a fair and effective LTCI system. This study aimed to evaluate the LTCI pilot by exploring the characteristics and care needs of claimants, and performance of the assessment tool. Methods A retrospective cross-sectional study in which claims data between July 2018 and March 2019 in the Guangzhou pilot was analyzed. LTCI claimants during the study period were included. The care needs were determined based on claimants’ physical function assessed by the Barthel Index and their medical conditions. Rasch analysis was used to explore the performance of the Barthel Index. Results Among 4810 claimants included, 4582 (95.3%) obtained LTCI benefits. Of these beneficiaries, 4357 (95.1%) were ≧ 60 years old, and 791 (17.3%) had dementia. Among 228 (4.7%) unsuccessful claimants, 22 (0.5%) had dementia. The prevalence of stroke was high in beneficiaries with (38.1%) or without dementia (56.6%), as well as in unsuccessful claimants with (40.9%) or without dementia (52.4%). Beneficiaries without dementia needed more support for basic activities of daily living and nursing care than those with dementia, while beneficiaries with dementia were more likely to be institutionalized. Five (22.7%) unsuccessful claimants with dementia and 48 (23.3%) unsuccessful claimants without dementia were disabled in at least two basic self-care activities. Regarding Barthel Index, Rasch analysis showed threshold disordering in “mobility” and “climbing stairs”, and the narrow interval was observed between all the adjacent categories of the ten items (

ObjectivesTo investigate differences in behavioral and psychological symptoms of dementia (BPSD) and caregiver distress caused between older adults with dementia living in the community and in nursing homes.DesignA comparative cross-sectional study.Setting and ParticipantsParticipants were recruited from outpatient clinics of a tertiary psychiatric hospital and dementia units of a nursing home in Guangzhou, China.MethodsNeuropsychiatric Inventory was used to assess symptoms and caregiver distress. Dementia severity was determined using the Clinical Dementia Rating.ResultsThis study included 157 community and 112 nursing home residents with dementia. Clinically significant symptoms (item score ≥ 4) were found in 88.5% of the former and 75% of the latter. Caregivers of 79.6% of the former and 26.8% of the latter reported that at least one of these caused them moderate-to-severe distress (distress score ≥ 3). Among the community patients, anxiety was the most frequent “very severe” symptom, while sleep disorders and agitation caused the most frequent “very severe” caregiver distress. After controlling for dementia severity and medication use, family caregiving remained an independent risk predictor for clinically significant symptoms and moderate-to-severe caregiver distress. The prediction of caregiver distress based on symptom scores varied across caregiver types and individual symptoms (R2 0.36–0.82). Group differences in clinically significant symptoms and moderate-to-severe caregiver distress showed at the stage of moderate-to-severe dementia.Conclusions and ImplicationsTailored management strategies to relieve family caregivers’ BPSD-induced distress are needed, especially at the stage of moderate-to-severe dementia. An effective service system should be established for supporting family caregivers to cope with BPSD.

Abstract Background Mucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis. MAC is diagnosed by WHO definition when the extracellular mucin is more than 50% of the lesion. We aimed at assessing the gene expression profiles of the CRCs with any mucinous features (> 5%) in a retrospective study. Methods The data of a 50-gene next generation sequencing (NGS) panel of 166 CRCs was analyzed and the gene mutational profile with morphologic features was correlated. Results We identified the different genetic mutation profiles between CRCs with and without mucinous component, but noticed a similar genetic profile between MACs and CRCs with mucinous component, irrespective of the percentage (if mucinous component more than 5%). The different genetic mutation profile related to MSI status was also identified between two groups of tumors. The most frequent mutations in CRCs with mucinous component are KRAS (28/49, 57.1%) and BRAF (19/49, 38.7%), PIK3CA (16/49, 32.6%), followed by APC (12/49, 24.5%) and TP53 (11/49, 22.5%). The combined mutation frequency of the two key factors in the EGFR signaling pathway, KRAS and BRAF, in the CRCs with and without mucinous component is 95.9 and 52.1%, respectively. Conclusions The dysregulation of EGFR pathway plays a critical role in the development of CRCs with mucinous component, irrespective of the percentage. The result suggested that the current cut off of 50% mucin component to define mucinous adenocarcinoma might be challengeable.

Abstract Background Perianal Paget’s disease (PPD) is rare and mostly described in clinical literature as case reports or small series. Methods We investigated the clinicopathologic and immunohistochemical features of PPD in a total of 13 cases retrieved from multiple academic institutions. Results The median age at diagnosis was 75 (range 50–86) years. Males were predominant with a male to female ratio of 2.25:1. Four (30.8%) cases were classified as primary PPD due to lack of synchronous or metachronous underlying malignancies, while nine (69.2%) were classified as secondary PPD with concurrent invasive adenocarcinoma (n = 8) or tubular adenoma with high-grade dysplasia (n = 1). Immunohistochemically, there is no differential expression of CK7 or CK20 in Paget’s cells between primary and secondary PPD; however, GCDFP-15 was only positive in primary PPD (3/3 vs. 0/6, P = 0.012), while CDX2 was only positive in secondary PPD (0/3 vs. 7/7, P = 0.008), suggesting different cell origin. All patients received local surgical resection with or without adjuvant therapy. After a median follow-up of 47 months, one patient with secondary PPD (7.7%) died of disease progression from underlying adenocarcinoma. Conclusions PPD occurs in elderly patients with male predominance and is frequently associated with underlying malignancies. Differential expression of CDX2 and GCDFP-15 may help distinguishing primary vs. secondary PPD, which is important for management as the presence of an underlying malignancy impacts clinical course and prognosis. Surgical excision remains the major treatment strategy for PPD. Long-term follow-up is required to monitor the disease recurrence and metastasis.

Abstract Inflammatory pseudotumor (IPT), also known as plasma cell granuloma, is a rare lesion of unknown etiology that occurs in many organs, especially in the lung. Here we report five cases of IPT arising in pulmonary artery mimicking chronic thromboembolic disease, not previously documented in the literature. Those cases were identified at our institute among over 2500 pulmonary endarterectomy (PEA) specimens acquired from 2000 to 2017. The cohort included three men and two women with a median age of 41 years (range: 23–54). All patients presented with dyspnea and radiologic findings of pulmonary artery thromboembolism, some concerning for intimal sarcoma. The duration between disease onset and PEA ranged from 6 months to approximately 3 years. Histologically, all cases showed proliferation of spindle cells with marked inflammatory infiltrates composed predominantly of plasma cells, histiocytes, and small lymphocytes. Ancillary studies were performed in each case and ruled out other possibilities, such as sarcoma, lymphoma, plasmacytoma, IgG4‐related disease, and infection. IPT arising in pulmonary artery presenting clinically as acute or chronic thromboembolic disease is very unusual, in which clinical data, radiographic findings, and histopathologic features have to be integrated for reaching the proper diagnosis.

ObjectivesTo evaluate application of the Barthel Index (BI) in assessing basic activities of daily living (ADL) of patients with dementia using Rasch analysis.DesignA multi-country cross-sectional study.Setting and ParticipantsNineteen long-term care facilities located in China, Japan, South Korea, and Thailand. A total of 644 patients with dementia were included.MethodsUnidimensionality, global and item fit, local dependence, person-item targeting, threshold disordering, and differential item functioning (DIF) were examined. Negative correlations between scores for DIF items and Neuropsychiatric Inventory Nursing Home version (NPI-NH) were evaluated.ResultsItem reliability (1.0) and person reliability (.88) were acceptable. The Rasch dimension explained 72.9% of the variance (Eigenvalue = 27), while the first contrast explained 6.6% (Eigenvalue = 2.4). The “mobility” was misfitting to the Rasch model (infit mean square = 1.86). The overall difficulty of the BI exceeded patients’ ability (person location = −2.27 logits). The “stairs climbing” and “mobility” showed narrow category thresholds (< 1.4 logits). The location of “controlling bladder” and “toilet use” overlapped. Removing “stairs climbing”, collapsing categories with narrow threshold widths in “mobility”, and combining “controlling bowel” and “controlling bladder” into one item, improved unidimensionality, and item fit of the scale. Only three items (“grooming”, “dressing”, and “toilet use”) were free from DIF across countries. The scores for “feeding” were negatively related to scores for “disinhibition” (r = −0.46, P < 0.01), and scores for “controlling bowel” were negatively related to scores for “disinhibition” (r = −0.44, P < 0.01), “agitation” (r = −0.32, P < 0.05), and “aggression” (r = −0.27, P < 0.01) in Japanese samples.Conclusions and ImplicationsThe performance of the BI for assessing patients with dementia might be compromised by misfit items, person–item mistargeting, measurement gaps, redundant items, narrow threshold width, and item bias. Mobility ability might not be helpful for determining capability of basic ADL in the patients. Comparisons of BI scores between countries should be undertaken with caution due to item bias. Neuropsychiatric symptoms might interact with basic ADL abilities of the patients. We will not suggest using the instrument in patients with dementia, without future refining to improve its performance.

The 2019 novel coronavirus disease (COVID-19), which is caused by the novel beta coronavirus, SARS-CoV-2, is currently prevalent all over the world, causing thousands of deaths with relatively high virulence. Like two other notable beta coronaviruses, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 can lead to severe contagious respiratory disease. Due to impaired cellular immunity and physiological changes, pregnant women are susceptible to respiratory disease and are more likely to develop severe pneumonia. Given the prevalence of COVID-19, it is speculated that some pregnant women have already been infected. However, limited data are available for the clinical course and management of COVID-19 in pregnancy. Therefore, we conducted this review to identify strategies for the obstetric management of COVID-19. We compared the clinical course and outcomes of COVID-19, SARS, and MERS in pregnancy and discussed several drugs for the treatment of COVID-19 in pregnancy.

The SMAD4 tumor suppressor gene product inhibits transforming growth factor-β-mediated signaling and is mutated in ~10% of colorectal carcinomas. The prognostic significance of SMAD4 mutations has been controversial. We studied the pathological and clinical characteristics of SMAD4-mutated intestinal adenocarcinomas using a retrospective case-control study design. Cases and controls were identified among 443 primary adenocarcinomas that had undergone next generation DNA sequencing (NGS) with the Ion AmpliSeq Cancer Hotspot Panel v2, which evaluates 50 cancer-related genes. Twenty-eight SMAD4-mutated (SMAD4m) patients were matched 1:2 with 56 consecutive SMAD4 wild-type (SMAD4wt) control patients from the same analysis stream. Compared with the SMAD4wt controls, the SMAD4m tumors were of higher stage (P = 0.026) and were more likely to feature mucinous differentiation (P = 0.0000), to occur in the setting of Crohn's disease (P = 0.0041), and to harbor concurrent RAS mutations (P = 0.0178). Tumor mucin content was significantly correlated with mutations involving the MH2 domain of the SMAD4 protein (P = 0.0338). Correspondence between mutation sites and morphology was demonstrated directly in a mixed adenocarcinoma and neuroendocrine tumor where SMAD4 mutations involving different protein domains were found in histologically disparate tumor regions despite both containing identical KRAS and TP53 mutations.

Summary: Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages. : In this report, Wilkinson and colleagues show that the conserved RNA degradation pathway—nonsense-mediated RNA decay (NMD)—is highly active in human embryonic stem cells (hESCs). They demonstrate that NMD degrades mRNAs encoding components of signaling pathways critical for primary germ-layer differentiation. hESC differentiation modulates NMD magnitude, which strongly influences mesoderm versus definitive endoderm cell fate.

This study used event-related potentials (ERPs) to investigate the effects of age on neural temporal dynamics of processing task-relevant facial expressions and their relationship to cognitive functions. Negative (sad, afraid, angry, and disgusted), positive (happy), and neutral faces were presented to 30 older and 31 young participants who performed a facial emotion categorization task. Behavioral and ERP indices of facial emotion processing were analyzed. An enhanced N170 for negative faces, in addition to intact right-hemispheric N170 for positive faces, was observed in older adults relative to their younger counterparts. Moreover, older adults demonstrated an attenuated within-group N170 laterality effect for neutral faces, while younger adults showed the opposite pattern. Furthermore, older adults exhibited sustained temporo-occipital negativity deflection over the time range of 200–500 ms post-stimulus, while young adults showed posterior positivity and subsequent emotion-specific frontal negativity deflections. In older adults, decreased accuracy for labeling negative faces was positively correlated with Montreal Cognitive Assessment Scores, and accuracy for labeling neutral faces was negatively correlated with age. These findings suggest that older people may exert more effort in structural encoding for negative faces and there are different response patterns for the categorization of different facial emotions. Cognitive functioning may be related to facial emotion categorization deficits observed in older adults. This may not be attributable to positivity effects: it may represent a selective deficit for the processing of negative facial expressions in older adults.

Mucoepidermoid carcinoma is the most common malignant tumor of the salivary gland. The oncocytic variant of mucoepidermoid carcinoma (OMEC) is rare and a small subset shows exclusive oncocytic morphology. Here we report an OMEC case of the parotid gland in a 74-year-old woman with exclusive oncocytes and rare mucocytes. The oncocytes showed diffuse nuclear positivity with p63 immunostaining. The MAML2 translocation was present, supporting the diagnosis of OMEC. Distinguishing OMEC with exclusive oncocytes from oncocytoma and oncocytic carcinoma can be very challenging for pathologists and is critical for proper clinical management. Our experience suggests that appropriate ancillary studies, especially the MAML2 translocation, may provide the essential evidence in difficult cases. Our literature review shows that the presence of mucocytes in an oncocytic neoplasm might be an important morphologic clue of OMEC.

Background/Aim: Lipomas are rare but the most common benign mesenchymal lesions of the gastrointestinal (GI) tract, composed of mature adipose cells. The "piggybacking lipoma" is formed by lipomas with overlying polypoid epithelial lesions, such as sessile serrated lesion, tubular adenoma, or hyperplastic polyp, and the literature on these lesions is limited. In this study, we systematically investigated the clinical, endoscopic, and pathologic characteristics of these unique lipomas. Patients and Methods: This is a single-institution retrospective study of gastrointestinal tract lipomas diagnosed from 2016-2021. Those with concurrent polypoid epithelial or mesenchymal lesions during the same endoscopic episode were included and reviewed in this study, and the lipomas were classified as "piggybacking lipoma" or "non-piggybacking lipoma" depending on whether the concurrent lesion was overlying the lipoma or was at a different location in the intestine. Demographic, clinical, and endoscopic data were obtained from electronic medical records. Results: A total of 100 lipomas with concurrent epithelial or mesenchymal lesions were included in this study. Among them, 21 cases were classified as "piggybacking lipoma" and 79 were classified as "non-piggybacking lipoma". Patients with piggybacking lipomas showed a female predilection, and were more likely to be symptomatic and less likely to exhibit classic endoscopic features of lipoma. Histologically, the piggybacking polyps showed overlying sessile serrated lesions (SSL) (76.2%) and tubular adenoma (TA) (19%), whereas the non-piggybacking group had differing characteristic lesions with TA (57.5%) and SSL (6.0%). Conclusion: Piggybacking lipomas are rare lipomas with overlying polypoid epithelial lesions, most commonly SSL. They present different clinical, endoscopic, and pathologic features compared to non-piggybacking lipomas. [ABSTRACT FROM AUTHOR]

Purpose: With technological progress, the integration of aged care with technology is a new challenge. This study developed a theoretical model of smart aged care in the community to meet the diverse needs of community‐dwelling older adults. Methods: This qualitative study recruited 22 participants from three communities in Chongqing, China. Through semi‐structured interviews and grounded theory, this study analyzed the needs of community‐dwelling older adults for smart aged care and identified strategies. Results: Nine categories were identified, including five need categories, three important factors, and one outcome objective. Furthermore, four health provider topics were proposed. Conclusions: Although the application of information technology has enhanced convenience and possibilities, its popularity and satisfaction are low. Information technology can be successfully introduced into the lives of community‐dwelling older adults only by truly understanding their needs. Implications of nursing practice: Smart aged care in the community has positive effects on nursing outcomes for older adults. This study's findings can help caregivers understand the various dimensions of the needs of community‐dwelling older adults and relevant influencing factors under smart aged care to increase its popularity and satisfaction. Furthermore, this can promote the integration of intelligent technology and manual services in nursing practice. [ABSTRACT FROM AUTHOR]