Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.

Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.

Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

Individual-level community-based social capital and depressive symptoms among older adults in urban China: the moderating effects of socioeconomic status.

OBJECTIVES: This study aimed to examine the moderating role of socioeconomic status in the association between community-based social capital-based on individual-level cognitive and structural social capital-and depressive symptoms among older adults in urban China. METHODS: Data were collected in 2020 through a community survey of 800 respondents aged 60 years and older living in Shijiazhuang and Tianjin. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Multiple-group analyses were conducted to analyze the data. RESULTS: Measurement models of cognitive social capital and structural social capital were established. Measurement invariance was established across different socioeconomic groups. Additionally, socioeconomic status significantly moderated the association between social capital and depressive symptoms. The association between cognitive social capital and depressive symptoms was statistically significant among respondents with relatively low incomes and high levels of education, whereas the association between structural social capital and depressive symptoms was significant only among those with relatively high incomes. CONCLUSION: Future social capital policies and interventions should adopt different strategies to provide services to older adults from different socioeconomic backgrounds. Furthermore, educational programs should promote the effects of cognitive social capital on depressive symptoms later in life.

Adverse childhood experiences and self-esteem among adolescents: The role of social capital and gender.

INTRODUCTION: Adverse childhood experiences have long-lasting effects on the self-esteem of adolescents. However, the extrinsic mechanism linking them to self-esteem, which is more modifiable, has rarely been examined. Therefore, this study examined the mediating roles of family, school, and peer social capital and the moderating role of gender in the association between adverse childhood experiences and adolescent self-esteem. METHODS: This study involved a cross-sectional survey of first- and second-grade students in the only high school in Wusu, Xinjiang Uygur Autonomous Region, China. Data were collected in May 2023. A sample of 2539 students (M = 16.84 years old; 55.65% female) was included. The measurement models of family, school, and peer social capital were constructed using confirmatory factor analysis. The mediating roles of the three types of social capital and the moderating role of gender were examined using mediation analysis and multiple-group analysis, respectively. RESULTS: Family, school, and peer social capital significantly mediated the relationship between adverse childhood experiences and adolescent self-esteem, and family social capital played the strongest role. Gender significantly moderated the direct effect of adverse childhood experiences on self-esteem. The direct effect was significant only among girls. CONCLUSIONS: This study underscores the protective role of social capital for self-esteem among adolescents in Northwestern China and similar areas with relatively limited social services. Comprehensive interventions promoting social capital, especially family social capital, should be conducted to enhance self-esteem among adolescents.

Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation.

The human rhomboid-5 homolog-1 (RHBDF1) is a multi-transmembrane protein present mainly on the endoplasmic reticulum. RHBDF1 has been implicated in the activation of epidermal growth factor receptor (EGFR)-derived cell growth signals and other activities critical to cellular responses to stressful conditions, but details of this activation mechanism are unclear. Here, we report a RHBDF1 mRNA transcript alternative splicing variant X6 (RHBDF1 X6 or RHX6) that antagonizes RHBDF1 activities. We found that while the RHBDF1 gene is marginally expressed in breast tumor-adjacent normal tissues, it is markedly elevated in the tumor tissues. In sharp contrast, the RHX6 mRNA represents the primary RHBDF1 variant in normal breast epithelial cells and tumor-adjacent normal tissues but is diminished in breast cancer cells and tumors. We demonstrate that, functionally, RHX6 acts as an inhibitor of RHBDF1 activities. We show that artificially overexpressing RHX6 in breast cancer cells leads to retarded proliferation, migration, and decreased production of epithelial-mesenchymal transition-related adhesion molecules. Mechanically, RHX6 is able to inhibit the maturation of TACE, a protease that processes pro-TGFα, a pro-ligand of EGFR, and to prevent intracellular transportation of pro-TGFα to the cell surface. Additionally, we show that the production of RHX6 is under the control of the alternative splicing regulator RNA binding motif protein-4 (RBM4). Our findings suggest that differential splicing of the RHBDF1 gene transcript may have a regulatory role in the development of epithelial cell cancers.

PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.

CD45- erythroid progenitor cells promote lymph node metastasis in gastric cancer by inducing a hybrid epithelial/mesenchymal state in lymphatic endothelial cells.

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.

Evaluation of Retinal Microvascular Features in Patients with Amblyopia Based on Optical Coherence Tomography Angiography: A Systematic Review and Meta-Analysis.

BACKGROUND: The performance of optical coherence tomography angiography (OCTA) in macular microvasculature of patients with amblyopia has been widely studied, but these studies have yielded different and controversial results. OBJECTIVES: The aim of this study is to investigate retinal microvascular features in patients with amblyopia undergoing OCTA. METHODS: PubMed, Embase, and Web of Science were searched for published articles comparing the retinal microvascular features between individuals with amblyopia and controls until April 2022. The mean difference with a 95% confidence interval was used to assess continuous variables. RESULTS: The analysis included 17 studies. The whole vessel density of the superficial capillary plexus (SCPVD) was lower in amblyopic eyes (AE) than in normal eyes (NE) in 3 × 3 mm2 scans, while the perifoveal vessel density of superficial and deep capillary plexus was lower in 6 × 6 mm2 scans. The whole, parafoveal vessel density of deep capillary plexus (DCPVD) and parafoveal SCPVD were lower in both scans. The comparison between AE and fellow eyes (FE) revealed no statistical difference in all quadrants except the parafoveal and perifoveal SCPVD and the foveal DCPVD. Additionally, SCPVD in all quadrants except the fovea and DCPVD in all quadrants except the parafoveal were higher in FE compared to NE. No significant difference was found in the foveal avascular area between AE and NE, AE and FE, or NE and FE. CONCLUSIONS: The retinal vessel density of superficial and deep capillary plexus in AE and FE was lower than in NE, and differences were more likely discovered using 6 × 6 mm2 scans. Consequently, OCTA might be explored as a diagnostic tool to identify and monitor patients with amblyopia.

A multiple-group analysis of social Capital and loneliness among community-dwelling older adults in urban China during the outbreak of the COVID-19 pandemic.

OBJECTIVES: The present study examined the moderating effects of family social capital on the relationship between community social capital and loneliness among older adults in urban Chinese communities during the COVID-19 outbreak period between January and March 2020.Method: We used quota sampling to recruit 472 community-dwelling older adults aged 60 years or older. A multiple-group analysis was applied to examine the proposed hypotheses.Results: Community-based cognitive social capital was significantly associated with both social and emotional loneliness among older adults with relatively low levels of family social capital. However, these associations were statistically nonsignificant among those with high family social capital levels. Community-based structural social capital was not associated with loneliness in either family social capital group.Conclusion: The findings highlight the role of cognitive social capital in reducing loneliness and support community social capital replacement theory in explaining the mechanism linking social capital to loneliness in later life in the context of the COVID-19 pandemic.

Suppression of matrix degradation and amelioration of disc degeneration by a 970-nm diode laser via inhibition of the p38 MAPK pathway in a rabbit model.

Intervertebral disc degeneration (IVDD) mainly manifests as an imbalance between the synthesis and degradation of cellular and extracellular matrix (ECM) components. The cytokine interleukin (IL)-1ß-induced inflammatory response of intervertebral discs causes ECM degradation. The aim of this study was to investigate the effects of a 970-nm diode laser therapy (DLT) on inflammatory cytokine IL-1ß and ECM degradation proteinases in nucleus pulposus (NP) tissues in a puncture-induced rabbit IVDD model. Thirty-six New Zealand white rabbits were randomly divided into six groups: the normal group, IVDD group, laser group, sham laser group, IVDD + anisomycin (p38MAPK signaling pathway agonist), and laser + anisomycin group. Effects of laser on IVDD progression were detected using radiographic and magnetic resonance imaging. Hematoxylin and eosin, Alcian blue, safranin O-fast green staining, western blotting, and immunohistochemistry staining were performed for the histological analysis and molecular mechanism underlying protection against puncture-induced matrix degradation in NP tissues by DLT. DLT reduced the degree of disc degeneration in the gross anatomy of the disc and increased the T2-weighted signal intensity of NP. Inflammatory cytokine IL-1ß levels in the disc were significantly reduced after DLT suppressed the matrix-degrading proteinases MMP13 and ADAMTS-5 and upregulated the protein expression of collagen II and aggrecan. Moreover, it inhibited the p38MAPK signaling pathway in NP tissues in a puncture-induced rabbit IVDD model. DLT reduced puncture-induced overexpression of inflammatory cytokines, mainly IL-1ß, thus inhibiting matrix degeneration of NP tissues and ameliorating IVDD. This may be related to inhibition of the p38 MAPK signaling pathway.

Prediction of childhood maltreatment and subtypes with personalized functional connectome of large-scale brain networks.

Childhood maltreatment (CM) has a long impact on physical and mental health of children. However, the neural underpinnings of CM are still unclear. In this study, we aimed to establish the associations between functional connectome of large-scale brain networks and influences of CM evaluated through Childhood Trauma Questionnaire (CTQ) at the individual level based on resting-state functional magnetic resonance imaging data of 215 adults. A novel individual functional mapping approach was employed to identify subject-specific functional networks and functional network connectivities (FNCs). A connectome-based predictive modeling (CPM) was used to estimate CM total and subscale scores using individual FNCs. The CPM established with FNCs can well predict CM total scores and subscale scores including emotion abuse, emotion neglect, physical abuse, physical neglect, and sexual abuse. These FNCs primarily involve default mode network, fronto-parietal network, visual network, limbic network, motor network, dorsal and ventral attention networks, and different networks have distinct contributions to predicting CM and subtypes. Moreover, we found that CM showed age and sex effects on individual functional connections. Taken together, the present findings revealed that different types of CM are associated with different atypical neural networks which provide new clues to understand the neurobiological consequences of childhood adversity.

Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer.

Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.

Efficacy of indwelling trocar therapy for postherpetic neuralgia: A retrospective study of an acupuncture method.

Postherpetic neuralgia (PHN) is a common complication of herpes zoster. As a kind of continuous acupuncture, indwelling trocar therapy (ITT) involves inserting a trocar into the skin and retaining the soft cannula in the body for 24 h. However, the efficacy and safety of ITT on PHN require further verification. In this study, the medical records of 122 patients with PHN were retrospectively analyzed. Patients were divided into the control group (patients who received conventional drug therapy) and the ITT group (patients who underwent ITT combined with conventional drug therapy). The Visual Analog Scale (VAS), Quality of Sleep (QS), 36-Item Short Form Health Survey (SF-36), dosage of drug and adverse events were analyzed at days 1, 3, 7, 14, 28, 90, and 180 after treatment. The total efficiency rate (TER) was analyzed after 6 months of follow-up. The VAS, QS and SF-36 scores in the ITT group improved substantially compared with those in the control group after 6 months of follow-up (p < 0.001). The average dosage of anticonvulsants and analgesics decreased significantly in the ITT group (p < 0.001). The TER in the control group was 52.46%, compared with 73.77% in the ITT group (p < 0.05). There were no adverse events, such as bleeding and infection, observed in the ITT group. For PHN patients, the combination of ITT and medicine therapy reduced VAS, improved quality of life, increased the efficiency rate, remarkably reduced the dosage of traditional medicine, and had no significant side effects. In addition, ITT was more effective in patients with a short duration of PHN than in chronic PHN patients.

Benzimidazole-Resistant Isolates with E198A/V/K Mutations in the ß-Tubulin Gene Possess Different Fitness and Competitive Ability in Botrytis cinerea.

Previous studies in Botrytis cinerea showed that resistance to methyl benzimidazole carbamates (MBCs) was mainly related to E198A/V/K and F200Y mutations of the ß-tubulin gene, and E198V was the dominant mutation in the resistant subpopulation in Hubei Province of China, indicating that resistant mutations might influence fitness. However, little is known about the effect of each E198A/V/K mutation on fitness. In this study, the fitness and competitive ability of isolates with E198A/V/K mutations were investigated. Results showed that E198A/V/K isolates and wild-type isolates shared similar fitness components in terms of virulence, sporulation, conidial germination, oxidative sensitivity, and sclerotial production and viability. However, slower mycelial growth at 4°C, higher sensitivity to 4% NaCl, and increased sclerotial production percentage at 4°C were observed in the isolates with E198V, E198K, and E198A mutations, respectively. Competitive analysis showed that the wild-type subpopulation became dominant after three disease cycles in the absence of fungicide selection pressure, whereas the resistant subpopulation seized the space of the sensitive subpopulation upon MBC application. Unexpectedly, the frequency of E198V isolates decreased dramatically after the first disease cycle with or without fungicide selection pressure. These results suggest that MBC-resistant isolates suffer little fitness penalty but possess competitive disadvantages in the absence of fungicide selection pressure. Under fungicide selection pressure, E198V isolates could not compete with E198A/K isolates. According to the current results, there is a great possibility that the E198V mutation will lose dominance in the future in China.

Analgesic effect of epidural anesthesia via the intervertebral foramen approach in percutaneous transforaminal endoscopic discectomy: a retrospective study.

BACKGROUND: Satisfactory intraoperative analgesia is critical for percutaneous transforaminal endoscopic discectomy (PTED). Local anesthesia (LA) and epidural anesthesia (EA) are recommended for PTED. LA alone does not achieve satisfactory pain management during PTED and other analgesics or sedatives are usually needed. Traditional EA, which involves implanting an epidural catheter through the midline or paramedian, has disadvantages such as difficulty in catheterization and increased preoperative preparation time. Rather than performing conventional EA, we injected local anesthetics through the intervertebral foramen during the puncture process, which we termed lumbar transforaminal EA (LTEA), and observed its feasibility and safety. This study aimed to conduct a comprehensive comparison of differences in analgesia between LA and LTEA in patients with PTED. METHODS: We performed a retrospective analysis of patients who underwent PTED between January 2018 and January 2021. Patients were divided into LA and LTEA groups. Data obtained from the electronic medical records included primary outcomes (visual analog scale [VAS] scores and anesthesia satisfaction rate) and secondary outcomes, including vital signs such as heart rate (HR), mean arterial pressure (MAP), total dosage of fentanyl, operation time, X-ray exposure time, Oswestry Disability Index (ODI) scores, and complications. RESULTS: In total, 160 patients (80 in each group) were analyzed in this study. The VAS scores for lumbar and leg pain were significantly lower in the LTEA group than in the LA group (P < 0.0001). The anesthesia satisfaction rate was 90.0% in the LTEA group and 72.5% in the LA group (P < 0.005). MAP and HR values in the LTEA group were significantly lower than those in the LA group (P < 0.05). The total dose of fentanyl in the LTEA group was significantly lower than that in the LA group (P < 0.05). As for ODI values, the average operation time, X-ray exposure time, and incidence of complications were not significantly different between the two groups (P > 0.05). CONCLUSIONS: LTEA simplifies the process of EA and can achieve a good analgesic effect intraoperatively without increasing the preoperative preparation time; thus, it may be adopted as an alternative mode of anesthesia during PTED surgery.

Reproductive Outbreaks of Sogatella furcifera Mediated by Overexpression of the Nuclear Receptor USP under Pressure from Triflumezopyrim.

Long-term pesticide-driven selection pressure is one of the main causes of insect outbreaks. In this study, we found that low doses of triflumezopyrim could increase the fecundity of white-backed planthoppers (Sogatella furcifera). By continuously screening 20 generations with a low dose of triflumezopyrim, a triflumezopyrim-resistant strain (Tri-strain, resistance ratio = 20.9-fold) was obtained. The average oviposition quantity and longevity of the Tri-strain (208.77 eggs and 21.31 days, respectively) were significantly higher than those of the susceptible strain (Sus-strain) (164.62 eggs and 17.85 days, respectively). To better understand the mechanism underlying the effects on reproduction, we detected the expression levels of several reproduction-related transcription factors in both the Tri- and Sus-strains. Ultraspiracle (USP) was significantly overexpressed in the Tri-strain. Knockdown of USP by RNAi severely inhibited the moulting process of S. furcifera and disrupted the development of female adult ovaries. Among the potential downstream target genes of USP, Kr-h1 (0.19-fold), Cht8 (0.56-fold) and GPCR A22 (0.31-fold) showed downregulated expression after USP-RNAi. In contrast, the expression of EcR (2.55-fold), which forms heterodimers with USP, was significantly upregulated. Furthermore, RNAi was performed on Kr-h1 in the Tri-strain, and the results show that larval moulting and the development of female adult ovaries were inhibited, consistent with the USP-RNAi results in S. furcifera. These results suggest that the transcription factors USP and Kr-h1 play important roles in the reproductive development of S. furcifera, and overexpression of USP and Kr-h1 in the Tri-resistant strain may result in reproductive outbreaks of pests.

The association between childhood conditions and heart disease among middle-aged and older population in China: a life course perspective.

BACKGROUND: Heart disease is a severe health problem among adult populations in China. The prevalence rates of heart disease increase with age. The pathogenic causes of heart disease are often related to conditions in early life. Using a nationally representative sample of adults aged 45 or older in China, we examined the association between childhood conditions and heart disease in later life from a life course perspective. METHODS: The data used in this study were derived from the life history module and 2015 wave of China Health and Retirement Longitudinal Study (CHARLS). Missingness were handled by multiple imputation, generating 20 complete datasets with a final sample of 19,800. Doctor-diagnosed heart disease was the main dependent variable. Respondents' conditions in childhood, adulthood, and older age were the independent variables (e.g., socioeconomic status, health, and health resources). Random-effects logistic regression models were conducted to test the hypotheses. RESULTS: A total of 16.6% respondents reported being diagnosed with heart disease by doctors. Regarding childhood socioeconomic status, 8.2% of the respondents considered that they were (a lot) better off than their neighbors, and 31.1% considered that their health status in childhood was better than their peers. More than 90% of respondents did not have severe illnesses during their childhood, and around 80.3% had access to health resources nearby in childhood. Lower socioeconomic status and poorer health conditions in childhood were associated with a greater likelihood of reporting doctor-diagnosed heart diseases, even after controlling for conditions in adulthood and older age (socioeconomic status: odds ratio (OR) = 0.947; self-rated health: OR = 0.917; severe illnesses: OR = 1.196). CONCLUSIONS: Along with chronic diseases (e.g., hypertension, diabetes, and dyslipidemia), unhealthy behaviors, overweight and obesity, poor childhood conditions should be considered as screening criteria to identify populations at risk of heart disease. Relevant preventive strategies and interventions should be developed from a life course perspective and conducted in communities by providing health education program among older population with low socioeconomic status, and encouraging early detection and treatment.

Topical Timolol Combined Intralesional Injection of Diprospan in the Treatment of Elevated Localized Mixed Infantile Hemangiomas and a Discussion for Proper Timing for Injection.

BACKGROUND: Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. PURPOSE: To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. METHODS: Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. RESULTS: Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ±â€Š1.50 months (range: 1.00-6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. CONCLUSION: Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.

Community-Based Cognitive Social Capital and Depressive Symptoms Among Older Adults in Urban China: The Moderating Role of Family Social Capital.

The present study examined the moderating role of family social capital in the relationship between community-based cognitive social capital and depressive symptoms among community-dwelling older adults in urban China. Cross-sectional data were derived from a community survey conducted in Suzhou, China, in late 2015. Data from 441 respondents were included in the final analysis. Multiple group analysis was used to test the hypotheses. The latent construct of community-based cognitive social capital was based on trust and reciprocity indicators. Measurement invariance was established across groups with high or low family social capital. The results show that family social capital had a moderation effect on the relationship between community-based cognitive social capital and depressive symptoms. The effects of community-based cognitive social capital on depressive symptoms were higher among those with low family social capital. The findings demonstrate the interplay between family and community-based cognitive social capital. Policy and intervention implications are discussed.

The 164 K, 165 K, and 167 K residues of VP1 are vital for goose parvovirus proliferation in GEFs based on PCR-based reverse genetics system.

BACKGROUND: Goose parvovirus (GPV) is the etiological agent of Derzsy's disease and is fatal for gosling. Research on the molecular basis of GPV pathogenicity has been hampered by the lack of a reliable reverse genetics system. At present, the GPV infectious clone has been rescued by transfection in the goose embryo, but the growth character of it is unclear in vitro. METHODS: In this study, we identified the full-length genome of GPV RC16 from the clinical sample, which was cloned into the pACYC177, generating the pIRC16. The recombinant virus (rGPV RC16) was rescued by the transfection of pIRC16 into goose embryo fibroblasts (GEFs). The rescued virus was characterized by whole genome sequencing, indirect immunofluorescence assays (IFA) and western blot (WB) using rabbit anti-GPV Rep polyclonal antibody as the primary antibody. Previously, we found the 164 K, 165 K, and 167 K residues in the 160YPVVKKPKLTEE171 are required for the nuclear import of VP1 (Chen S, Liu P, He Y, et al. Virology 519:17-22). According to that, the GPV infectious clones with mutated K164A, K165A, or K167A in VP1 were constructed, rescued and passaged. RESULTS: The rGPV RC16 has been successfully rescued by transfection of pIRC16 into the GEFs and can proliferate in vitro. Furthermore, the progeny virus produced by pIRC16 transfected cells was infectious in GEFs. Moreover, mutagenesis experiments showed that the rGPV RC16 with mutated 164 K, 165 K and 167 K in VP1 could not proliferate in GEFs based on the data of IFA and WB in parental virus and progeny virus. CONCLUSIONS: The rGPV RC16 containing genetic maker and the progeny virus are infectious in GEFs. The 164 K, 165 K, and 167 K of VP1 are vital for the proliferation of rGPV RC16 in vitro.