Advancements in osteosarcoma management: integrating immune microenvironment insights with immunotherapeutic strategies.

Osteosarcoma, a malignant bone tumor predominantly affecting children and adolescents, presents significant therapeutic challenges, particularly in metastatic or recurrent cases. Conventional surgical and chemotherapeutic approaches have achieved partial therapeutic efficacy; however, the prognosis for long-term survival remains bleak. Recent studies have highlighted the imperative for a comprehensive exploration of the osteosarcoma immune microenvironment, focusing on the integration of diverse immunotherapeutic strategies-including immune checkpoint inhibitors, tumor microenvironment modulators, cytokine therapies, tumor antigen-specific interventions, cancer vaccines, cellular therapies, and antibody-based treatments-that are directly pertinent to modulating this intricate microenvironment. By targeting tumor cells, modulating the tumor microenvironment, and activating host immune responses, these innovative approaches have demonstrated substantial potential in enhancing the effectiveness of osteosarcoma treatments. Although most of these novel strategies are still in research or clinical trial phases, they have already demonstrated significant potential for individuals with osteosarcoma, suggesting the possibility of developing new, more personalized and effective treatment options. This review aims to provide a comprehensive overview of the current advancements in osteosarcoma immunotherapy, emphasizing the significance of integrating various immunotherapeutic methods to optimize therapeutic outcomes. Additionally, it underscores the imperative for subsequent research to further investigate the intricate interactions between the tumor microenvironment and the immune system, aiming to devise more effective treatment strategies. The present review comprehensively addresses the landscape of osteosarcoma immunotherapy, delineating crucial scientific concerns and clinical challenges, thereby outlining potential research directions.

AQP8 Modulates Mitochondrial H2O2 Transport to Influence Glioma Proliferation.

BACKGROUND: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. MATERIALS AND METHODS: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. RESULT: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. CONCLUSIONS: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.

New Constraints on Exotic Spin-Spin-Velocity-Dependent Interactions with Solid-State Quantum Sensors.

We report new experimental results on exotic spin-spin-velocity-dependent interactions between electron spins. We designed an elaborate setup that is equipped with two nitrogen-vacancy (NV) ensembles in diamonds. One of the NV ensembles serves as the spin source, while the other functions as the spin sensor. By coherently manipulating the quantum states of two NV ensembles and their relative velocity at the micrometer scale, we are able to scrutinize exotic spin-spin-velocity-dependent interactions at short force ranges. For a T-violating interaction, V_{6}, new limits on the corresponding coupling coefficient, f_{6}, have been established for the force range shorter than 1 cm. For a P,T-violating interaction, V_{14}, new constraints on the corresponding coupling coefficient, f_{14}, have been obtained for the force range shorter than 1 km.

Improved Limits on an Exotic Spin- and Velocity-Dependent Interaction at the Micrometer Scale with an Ensemble-NV-Diamond Magnetometer.

Searching for exotic interactions provides a path for exploring new particles beyond the standard model. Here, we used an ensemble-NV-diamond magnetometer to search for an exotic spin- and velocity-dependent interaction between polarized electron spins and unpolarized nucleons at the micrometer scale. A thin layer of nitrogen-vacancy electronic spin ensemble in diamond is utilized as both the solid-state spin quantum sensor and the polarized electron source, and a vibrating lead sphere serves as the moving unpolarized nucleon source. The exotic interaction is searched by detecting the possible effective magnetic field induced by the moving unpolarized nucleon source using the ensemble-NV-diamond magnetometer. Our result establishes new bounds for the coupling parameter f_{⊥} within the force range from 5 to 400 µm. The upper limit of the coupling parameter at 100 µm is |f_{⊥}|≤1.1×10^{-11}, which is 3 orders of magnitude more stringent than the previous constraint. This result shows that NV ensemble can be a promising platform to search for hypothetical particles beyond the standard model.

Upregulation of FAM50A promotes cancer development.

FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

The application and research progress of anti-angiogenesis therapy in tumor immunotherapy.

Tumor immunotherapy, as the focus of scientific research and clinical tumor treatment in recent years, has received extensive attention. Due to its remarkable curative effect and fewer side effects than traditional treatments, it has significant clinical benefits for the treatment of various advanced cancers and can improve cancer patient survival in the long term. Currently, most patients cannot benefit from immunotherapy, and some patients may experience tumor recurrence and drug resistance even if they achieve remission overcome. Numerous studies have shown that the abnormal angiogenesis state of tumors can lead to immunosuppressive tumor microenvironment, which affects the efficacy of immunotherapy. Actually, to improve the efficacy of immunotherapy, the application of anti-angiogenesis drugs to normalize abnormal tumor vessel has been widely confirmed in basic and clinical research. This review not only discusses the risk factors, mechanisms, and effects of abnormal and normalized tumor angiogenesis state on the immune environment, but summarizes the latest progress of immunotherapy combined with anti-angiogenic therapy. We hope this review provides an applied reference for anti-angiogenesis drugs and synergistic immunotherapy therapy.

New constraints on exotic spin-dependent interactions with an ensemble-NV-diamond magnetometer.

Laboratory search of exotic interactions is crucial for exploring physics beyond the standard model. We report new experimental constraints on two exotic spin-dependent interactions at the micrometer scale based on ensembles of nitrogen-vacancy (NV) centers in diamond. A thin layer of NV electronic spin ensembles is synthesized as the solid-state spin quantum sensor, and a lead sphere is taken as the interacting nucleon source. Our result establishes new bounds for two types of exotic spin interactions at the micrometer scale. For an exotic parity-odd spin- and velocity-dependent interaction, improved bounds are set within the force range from 5 to 500 µm. The upper limit of the corresponding coupling constant [Formula: see text] at 330 µm is more than 1000-fold more stringent than the previous constraint. For the P, T-violating scalar-pseudoscalar nucleon-electron interaction, improved constraints are established within the force range from 6 to 45 µm. The limit of the corresponding coupling constant [Formula: see text] is improved by more than one order of magnitude at 30 µm. This work demonstrates that a solid-state NV ensemble can be a powerful platform for probing exotic spin-dependent interactions.

AQP8 may affect glioma proliferation and growth by regulating GSK-3ß phosphorylation and nuclear transport of ß-catenin.

PURPOSE: The purpose of this work is to examine the impact of AQP8 on the proliferation and development of human glioma cell lines A172 and U251 and to determine if aquaporin 8 (AQP8) is associated with GSK-3ß phosphorylation and nuclear transport of ß-catenin in the Wnt signaling pathway. METHODS: AQP8 knockdown cell lines were constructed using a CRISPR/Cas9 double vector lentivirus infection. SAM/dCas9 was used to construct AQP8 overexpression cell lines and the CV084 lentivirus vector was used to construct AQP8 rescue cell lines. AQP8 and its mRNA, and phosphorylated GSK-3ß, ß-catenin, and other related proteins, were detected using western blot and qRT-PCR. Glioma cell apoptosis was detected using Hoechst 33342 dye. The migration of glioma cells was discovered using a wound healing assay. ß-catenin localization in cells was detected using immunofluorescence staining. RESULTS: The proliferative and migratory capacities of A172 and U251 cells were significantly enhanced after AQP8 overexpression. The Wnt signaling pathways appeared to have higher levels of phosphorylated GSK-3ß and ß-catenin, and a rise in the fluorescence intensity ratio of ß-catenin in the nucleus and cytoplasm, which suggests that ß-catenin translocated into the nucleus, while AQP8 knockdown produced the opposite effect. Further, overexpression of AQP8 in AQP8 knockdown cell lines rescued the reduction of related protein levels caused by AQP8 knockdown. CONCLUSION: High AQP8 expression promotes proliferation and growth of glioma cells, a process associated with phosphorylation of GSK-3ß and nuclear translocation of ß-catenin.

The association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services: 2008 ~ 2018.

BACKGROUND: The changes in demographic and family structures have weakened the traditional norms of filial piety and intergenerational relationships dramatically. This study aims to examine the dynamic association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services. METHODS: Data was derived from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), which is a longitudinal survey of a nationally representative sample of individuals aged 60 and over. Random effects model was used to assess the association between financial support and informal care provision of adult children to their parents. RESULTS: It was found that financial support showed an upward trend while informal care provision showed a download trend from 2008 to 2018. The result indicated a significant and negative association between financial support and informal care provision of adult children to their parents (B = -0.500, 95% confidence interval (CI) = -0.761 to -0.239). And the association was significant among elderly people who were from urban areas (B = -0.628, 95% CI = -0.970 to -0.287), co-resided with adult children (B = -0.596, 95% CI = -0.939 to -0.253), and had community-based services (B = -0.659, 95% CI = -1.004 to -0.315). CONCLUSION: Financial support was negatively associated with informal care provision of adult children to their parents in China, and the association has differences in household registration, residence arrangement and community-based care services. It is suggested that policymakers should prioritize planning interventions for elderly care services and establish a family caregiver support system.

Upregulation of TUBG1 expression promotes hepatocellular carcinoma development.

Tubulin γ-1 (TUBG1) is a highly conserved component of the centrosome and its deregulation is involved in the development of several types of cancer. However, the role of TUBG1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TUBG1 was upregulated in human HCC cells and tissues and that TUBG1 upregulation was associated with promoter hypomethylation in HCC tissues. TUBG1 knockdown suppressed the proliferation, invasion, and migration of HCC cells. While TUBG1 expression was positively correlated with CD4 + memory T lymphocyte infiltration, it was negatively correlated with CD4 + regulatory T-cell infiltration in human HCC tissues. Furthermore, TUBG1 expression was positively correlated with the expression of genes involved in cell division. Noticeably, high expression of TUBG1 was associated with poor prognosis in patients with HCC. Overall, our findings revealed that TUBG1 promotes hepatocarcinogenesis by increasing proliferation, invasion, and migration of HCC cells and may regulate T lymphocyte infiltration. The current findings provide important insights into TUBG1 regulation in HCC, which could provide new therapeutic targets for hepatocarcinoma which has a very high incidence and mortality rate worldwide.

Association between mild cognitive impairment and falls among Chinese older adults: the mediating roles of balance capacity and depressive symptoms.

BACKGROUND: This study aimed to examine the association between mild cognitive impairment (MCI) and the follow-up risk of falls among Chinese older adults, exploring the mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. METHODS: A total of 5482 adults aged 60 years and above from waves 2015 and 2018 of the China Health and Retirement Longitudinal Study were included for analysis. Cognition was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status. Depressive symptoms were assessed with the Centre for Epidemiological Studies Depression Scale. Logistic regression models were used to estimate the association between MCI and falls. Mediation analysis was employed to explore the potential mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. RESULTS: MCI was significantly associated with the risk of falls (OR 1.259, 95% CI 1.080 to 1.467). Balance capacity and depressive symptoms played parallel mediating roles in the association between MCI and falls, and the mediating effects were 0.004 (95% CI 0.003 to 0.024) and 0.010 (95% CI 0.004 to 0.016), respectively. CONCLUSIONS: It is necessary to screen for and recognise MCI in order to prevent falls among older adults. More efforts should be made to improve balance capacity and relieve depressive symptoms to reduce the risk of falls among older adults with MCI.

Increased Expression of NXPH4 Correlates with Immune Cell Infiltration and Unfavorable Prognosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading malignant carcinomas. Despite the advancement in the treatment for HCC, such as precise hepatectomy, radiotherapy, transarterial therapies, chemotherapy, targeted treatments, and immunotherapy, the 5-year overall survival rate of HCC is extremely low. Hence, novel biomarkers are urgently needed for advancing the therapy and prognosis of HCC. Neurexophilin 4 (NXPH4) is a neuropeptide-like glycoprotein. The study is designed to investigate the function of NXPH4 in HCC through a comprehensive bioinformatics analysis. NXPH4 expression status and prognostic values were analyzed via multiple datasets, such as TCGA, GEO, and ICGC. The association between NXPH4 and immune cell infiltration was estimated by TIMER, TISIDB, and CIBERSORT. In vitro, we explored the biological function of NXPH4 in JHH7 and SNU182 cells through knocking down the expression of NXPH4 via siRNA. In general, NXPH4 was predominantly upregulated in HCC tumors, and increased NXPH4 expression predicted unfavorable prognosis. The gene enrichment analysis displayed that NXPH4 was related with metabolic pathways. NXPH4 expression was correlated with immune cell infiltration. NXPH4 knockdown significantly suppressed proliferation, migration, and invasion of JHH7 and SNU182 cells. This study suggested that the upregulation of NXPH4 is associated with adverse prognosis and immune cell infiltration in HCC. NXPH4 could be a novel biomarker of unfavorable prognosis and an underlying target for immunotherapy in HCC.

Understanding the effect of retirement on health behaviors in China: Causality, heterogeneity and time-varying effect.

Retirement is an important turning point during the course of life, but few studies have examined the effects of retirement on a broad range of health behaviors in China. We use the longitudinal data of the China Health and Nutrition Survey (CHNS) from 2004 to 2015 to conduct empirical analysis. Fuzzy discontinuity regression was used to assess the association between retirement and health behaviors in the entire sample and subgroups based on gender and education. A time-varying effect model was used to measure the anticipatory effect, immediate effect and lag effect of retirement. We observed that the transition to retirement was associated with healthier lifestyle habits, such as reduced smoking and alcohol consumption and increased exercise motivation. However, the transition was associated with worse sedentary behavior. No significant statistical association was found between retirement and sleep duration. Men and those with higher education levels are more likely to experience the impact of retirement. The anticipatory effect suggests that as the statutory pension age is predictable, workers adjust their behaviors 4 and 5 years before retirement. The lagged effect indicates that it takes time to develop new habits; thus, retirees change their behaviors 2-3 years after retirement. The paper discusses possible reasons for our findings and proposes several policy implications from the perspectives of the government and society to facilitate the realization of healthy aging.

The association between reproductive history and the multidimensional health of older adults in rural China and its gender differences: Evidence from the Chinese longitudinal healthy longevity survey.

Background: Few studies have examined the association between reproductive history and the multidimensional health of older adults with more diverse reproductive histories and poorer health status in rural China. The purpose of this study is to explore the effect of parity, sex ratio of children and late childbearing on multidimensional health and its gender differences. Methods: The analytical sample consisted of 3,377 older adults in rural China who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018. Linear regression models were applied to estimate the relationship between reproductive history and multidimensional health, with separate models for each indicator of health outcomes. Results: Older adults in rural areas with greater parity were more likely to have better cognitive function (ß = 0.409, 95% CI: 0.255-0.563), fewer Activities of Daily Living (ADL) limitations (ß = -0.085, 95% CI: -0.137 to -0.034) and symptoms of depression (ß = -0.396, 95% CI: -0.577 to -0.216). The social mechanism of intergenerational support from children later in life partly explained the positive effect of parity. Late childbearing had negative effects on cognitive function (ß = -1.220, 95% CI: -1.895 to -0.545), ADL (ß = 0.253, 95% CI: 0.028-0.478) and symptoms of depression (ß = 1.025, 95% CI: 0.237-1.812). Women were more likely to be influenced by the positive effect of parity; the association between late childbearing and health was only significant in the male group. Conclusions: Parity and late childbearing are associated with cognitive function, activities of daily living, and symptoms of depression in the older adults in rural China. Older adults with more children might be in better health, and this finding is especially significant in women. However, late childbearing had a negative effect on multidimensional health, especially for men. The social mechanism and gender differences between reproductive history and health need to be further explored.

Optimism and survival: health behaviors as a mediator-a ten-year follow-up study of Chinese elderly people.

BACKGROUND: Optimism-the generalized expectation that good things will happen-is a promising health asset. Mounting evidence indicates that there are specific associations between optimism and survival rates. However, for public health purposes, it is critical to consider whether the relationship between optimism and survival holds for older adults as a whole and to explore the role of health behaviors as potential mediators. METHODS: Prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Optimism was measured in 2008, and survival was measured by survival time of the interviewees during the whole observation period from 2008 to 2018. Cox proportional hazard models were employed to evaluate the association between optimism and survival among the elderly. The mediating effect analysis method was used to explore the potential mediating role of health behaviors on the association between optimism and survival. RESULTS: Compared to less optimistic older adults, optimistic individuals were associated with lower odds of mortality (HR = 0.94, 95% CI = 0.89 - 0.99). Health behaviors are key elements that play a positive role in survival (HR = 0.95, 95% CI = 0.94 - 0.96). Health behaviors played an intermediary role in the relationship between optimism and mortality, and the mediating effect was -0.005. CONCLUSIONS: Optimism and health behaviors were broadly and robustly associated with a lower risk of mortality. Health behaviors mediate the relationship between optimism and mortality. Appropriate intervention should be carried out on optimism and health behaviors among elderly people to improve the likelihood of health in aging.

The association between falls and anxiety among elderly Chinese individuals: The mediating roles of functional ability and social participation.

BACKGROUND: Elderly individuals who experience falls suffer from higher levels of anxiety because of physical or mental injury. This study examined the association between falls and anxiety among elderly Chinese individuals. It also explored the mediating roles of functional ability and social participation in the link between falls and anxiety. METHODS: The analytical sample included 8233 elderly people aged 60 and above, and prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Anxiety was evaluated by a 7-item Generalized Anxiety Disorder (GAD-7) scale, and falls were determined by self-report. The association between falls and anxiety was assessed by linear regression. Mediation analysis was used to explore the potential mediating roles of functional ability and social participation on the association between falls and anxiety. RESULTS: Suffering falls predicted higher anxiety levels among elderly individuals (B = 0.608, 95% CI: 0.471, 0.746). Functional ability and social participation play partial mediating roles in the association between falls and anxiety, and the mediating effects were 0.036 (95% CI: 0.020, 0.058) and 0.005 (95% CI: 0.003, 0.014), respectively. The serial mediating effect of functional ability and social participation on the association between falls and anxiety was 0.003 (95% CI: 0.002, 0.005). LIMITATIONS: This study is based upon cross-sectional data, which limit inferring causality. CONCLUSIONS: This study suggests that policy-makers should explore how to encourage elderly individuals who experience falls to restore functional ability and participate in appropriate social activities to alleviate anxiety.

Ultrasonic Interfacial Engineering of MoS2 -Modified Zn Single-Atom Catalysts for Efficient Osteomyelitis Sonodynamic Ion Therapy.

Osteomyelitis is considered as the most serious bone infection, which can lead to the bone destruction or fatal sepsis. Clinical treatments through frequent antibiotics administration and surgical debridement bring inevitable side effects including drug-resistance and disfigurements. It is urgent to develop an antibiotics-free and rapid strategy to treat osteomyelitis. Herein, a bifunctional sonosensitizer that consists of porphyrin-like Zn single-atom catalysts (g-ZnN4 ) and MoS2 quantum dots is developed, which exhibits excellent sonodynamic antibacterial efficiency and osteogenic ability. It is found that the construction of heterogeneous interfaces of g-ZnN4 -MoS2 fully activates the adsorbed O2 due to the increased interface charge transfer, enhanced spin-flip, and reduced activation energy of O2 . The generated 1 O2 can kill methicillin-resistant Staphylococcus aureus (MRSA) with an antibacterial efficiency of 99.58% under 20 min of ultrasound (US) irradiation. The Zn single atoms immobilized in g-ZnN4 can be released steadily in the form of Zn2+ for 28 days within safe concentration, realizing the great osteoinductive ability of such a sonosensitizer. For the treatment of MRSA-infected osteomyelitis, the inflammation and bone loss can be significantly suppressed through sonodynamic ion therapy. This work provides another strategy for developing high efficiency sonosensitizer through ultrasound interfacial engineering.

Effects of two inhibitors of metabolic glutamate receptor 5 on expression of endogenous homer scaffold protein 1 in the auditory cortex of mice with tinnitus.

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.

Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review.

BACKGROUND: Kartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations in DNAH5. Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome. CASE PRESENTATION: A 7-year-old female patient presented with runny nose of 6 years duration and recurrent cough with phlegm of 2 years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations in DNAH5, NM_001369:c.12813G > A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarize DNAH5 mutations in pediatric patients with Kartagener syndrome across different ethnic groups. CONCLUSIONS: Our study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations in DNAH5 were identified and validated in a pediatric patient with Kartagener syndrome.

The Association between Widowhood and Cognitive Function among Chinese Elderly People: Do Gender and Widowhood Duration Make a Difference?

Few studies have examined the effects of widowhood on cognitive function in Chinese elderly individuals. We conducted a longitudinal study to assess the association between widowhood and cognitive function and further explored gender differences in this association and the impact of widowhood duration. The analytical sample consisted of 5872 Chinese elderly people who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and were followed up from 2005 to 2014. We used the Chinese version of the Mini-Mental State Examination (MMSE) to assess cognitive function. Widowhood duration was calculated from the self-reported year at which the spouse passed away. Multilevel growth models were employed to estimate the association between widowhood and cognitive function while adjusting for many demographic and socioeconomic characteristics. Widowhood status was associated with cognitive decline among Chinese elderly individuals after adjusting for covariates (B = -0.440, 95% CI -0.727 to -0.152), and this association was only statistically significant among men (B = -0.722, 95% CI -1.104 to -0.339). Being widowed for 5 years or less (B = -0.606, 95% CI -1.112 to -0.100), 16-20 years (B = -0.937, 95% CI -1.685 to -0.190), and 21+ years (B = -1.401, 95% CI -1.967 to -0.834) predicted worse cognitive function in men, while being widowed for more than 21+ years (B = -0.655, 95% CI -1.186 to -0.124) was associated with cognitive decline in women. More attention should be directed towards widowed men and long-term widowed elderly individuals.