Association between short-term air pollution exposure and perturbation in thyrotropin levels in 1.38 million Chinese women: A national longitudinal analysis, 2014-2019.

Prevalence of subclinical hypothyroidism substantially increased during the last decade in China, which has been commonly/clinically diagnosed as elevation in thyrotropin (thyroid-stimulating hormone [TSH]). Tobacco smoke containing toxic substances has been linked to thyroid dysfunction; however, data on perturbation of TSH following air pollution exposure in human has not been assessed at nationwide population level. We investigated the longitudinal impact of daily ambient air pollution estimated at residential level on serum TSH in 1.38 million women from China's 29 mainland provinces between 2014 and 2019. We observed that particulate matter with aerodynamic diameter ≤ 10 and ≤ 2.5 µm (PM10, PM2.5) and nitrogen dioxide (NO2) at cumulative lag 0-7 days of exposure were associated with percent elevations in TSH (0.88% [95% CI: 0.71, 1.05] per [interquartile range, IQR: 54.8 µg/m3] of PM10; 0.89% [95% CI, 0.71, 1.07] per IQR [40.3 µg/m3] of PM2.5; 2.01% [95% CI: 1.81, 2.22] per IQR [27.4 µg/m3] of NO2). Greater associations were observed in participants living in areas with ≥adequate iodine intake and those with low BMI levels and high inflammation status. Our results suggest that increased concentrations of recent ambient air pollutants at exposure ranges commonly encountered in Asia were associated with increases in TSH, supporting disturbing role of short-term air pollution exposure on the regulation of thyroid hormone homeostasis.

GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21.

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.

A Mendelian randomization-based approach to explore the relationship between leukocyte counts and breast cancer risk in European ethnic groups.

Exploring the potential association between peripheral blood leukocyte counts and breast cancer risk by Mendelian randomization (MR) analysis methods. Genetic data related to peripheral blood sorting counts of leukocytes were collected from a genome-wide association study by Blood Cell Consortium (BCX). Single nucleotide polymorphic loci predicting peripheral blood sorting counts of these leukocytes were selected as instrumental variables according to the correlation assumption, independence assumption and exclusivity assumption of MR. The data on breast cancer and its subtypes were obtained from Breast Cancer Association Consortium (BCAC) and FinnGen Consortium. In this study, the Inverse-Variance Weighted (IVW), Weighted Median, MR-Egger, Maximum Likelihood (ML), MR-PRESSO and Constrained Maximum Likelihood and Model Averaging (cML-MA) methods of random effects models were used for MR analysis. Cochran's Q analysis, and MR-Egger intercept analysis were applied for sensitivity analysis. IVW and cML-MA were considered the primary analytical tools, and the results of the other 4 MRs were used as complementary and validation. The results suggest that there is no significant causal relationship between leukocyte count and breast cancer risk (IVW OR = 0.98 [95% CI: 0.93-1.03], p-value = 0.35; CML-MA OR = 1.01 [95% CI: 0.98-1.05], p-value = 0.51). In addition, we analyzed whether there was a potential correlation between the five main types of categorized leukocyte counts and different breast cancer subtypes. We did not find significant evidence to support a significant correlation between leukocyte counts and breast cancer subtypes.

Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients.

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. RESULTS: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9-16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°-25°), 40 (13.8%) moderate (25°-50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07-1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4-3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23-40) postoperatively. CONCLUSION: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer after curative surgery.

BACKGROUND: The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer has not been exhaustively investigated. Thus, the present study was performed to evaluate the effect of sarcopenia on the outcome of patients with left-sided colon and rectal cancer. METHODS: Patients with pathologically diagnosed stage I, II and III left-sided colon or rectal cancer who had undergone curative surgery between January 2008 and December 2014 were retrospectively reviewed. The psoas muscle index (PMI) identified by 3D-image analysis of computed tomographic images was the criterion used to diagnose sarcopenia. The cut-off value recommended by Hamaguchi (PMI value < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women) was adopted to confirm the diagnosis of sarcopenia. According to the PMI, each patient was divided into the sarcopenia group (SG) or the nonsarcopenia group (NSG). Then, the SG was compared with the NSG in terms of postoperative outcomes. RESULTS: Among the 939 patients included, 574 (61.1%) were confirmed to have preoperative sarcopenia. Initially, it was demonstrated that the SG was not significantly different from the NSG in terms of most baseline characteristics except for a lower body mass index (BMI) (P < 0.001), a larger tumour size (P < 0.001) and more weight loss (more than 3 kg in the last three months) (P = 0.033). The SG had a longer hospital stay after surgery (P = 0.040), more intraoperative blood transfusions (P = 0.035), and higher incidence of anastomotic fistula (P = 0.027), surgical site infection (SSI) (P = 0.037) and hypoalbuminemia (P = 0.022), 30-day mortality (P = 0.042) and 90-day mortality (P = 0.041). The SG had significantly worse overall survival (OS) (P = 0.016) and recurrence-free survival (RFS) (P = 0.036) than the NSG. Subsequently, Cox regression analysis revealed that preoperative sarcopenia was an independent predictive factor for worse OS (P = 0.0211, HR = 1.367, 95% CI: 1.049-1.782) and RFS (P = 0.045, HR = 1.299, 95% CI: 1.006-1.677). CONCLUSION: Preoperative sarcopenia adversely affects the outcome of patients with left-sided colon and rectal cancer, and preoperative nutrition supplementation may help us improve their long-term and short-term outcomes.

Driving forces and recovery potential of the macrophyte decline in East Taihu Lake.

Macrophytes are of key importance to the structure and ecological services of shallow lakes and are sensitive to anthropogenic and natural perturbations. Ongoing eutrophication and hydrological regime change affect macrophytes through changes in water transparency and water level, which lead to a dramatic decrease in bottom light availability. Here an integrated dataset (2005-2021) of multiple environmental factors is used to demonstrate the driving forces and recovery potential of the macrophyte decline in East Taihu Lake by using a critical indicator, which is the ratio of the Secchi disk depth to the water depth (SD/WD). The macrophyte distribution area showed a remarkable decrease from 136.1 ± 9.7 km2 (2005-2014) to 66.1 ± 6.5 km2 (2015-2021). The macrophyte coverage in the lake and in the buffer zone decreased by 51.4% and 82.8%, respectively. The structural equation model and correlation analysis showed that the distribution and coverage of macrophytes decreased with the decrease in the SD/WD over time. Moreover, an extensive hydrological regime change, which caused a sharp decrease in SD and an increase in the water level, is likely to be the driving force that brought about the decline of macrophytes in this lake. The proposed recovery potential model shows that the SD/WD has been low in recent years (2015-2021), and that this SD/WD cannot ensure the growth of submerged macrophytes and is unlikely to ensure the growth of floating-leaved macrophytes, especially in the buffer zone. The approach developed in the present study provides a basis for the assessment of macrophyte recovery potential and the management of ecosystems in shallow lakes that suffer from macrophyte loss.

Effectiveness of post-mastectomy adjuvant chemotherapy for the treatment of patients with prognostic stage IB breast cancer: A SEER-based study.

BACKGROUND: Adjuvant chemotherapy (AC) is an important, effective treatment for breast cancer. This study evaluates the effectiveness of post-mastectomy AC in treating patients with prognostic stage IB breast cancer. METHOD: We conducted a retrospective cohort-based study using Surveillance, Epidemiology, and End-Results database. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated using the Kaplan-Meier method. Multivariate Cox risk models were used to identify the impact of AC. Stratified analysis was performed according to molecular subtypes, anatomic stages, and other risk factors to evaluate the effect of AC on survival. RESULTS: 28,825 women diagnosed with prognostic stage IB breast cancer were included. The 5-year OS was significantly higher in AC group than in non-adjuvant chemotherapy (NAC) group (P < 0.0001); however, the 5-year BCSS in AC group was significantly lower than in NAC group (P = 0.039). Multivariate analysis revealed that AC was a favorable prognostic factor for OS (P < 0.001), but not BCSS (P = 0.407). AC was not an independent prognostic factor for BCSS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR[+]/HER2[-]) subtype or pT1a-1b/N0-1 stage with HER2 overexpression (HER2[+]) subtype, regardless of whether HR was positive or negative (P > 0.05). Meanwhile, AC is not an independent prognostic factor for OS and BCSS in patients with lymph node micrometastases. CONCLUSION: Our study demonstrates that patients with prognostic stage IB do not fully benefit from AC. Individualized treatment management is required for patients with pT1a-1b/N0-1 tumors, lymph node micrometastases, or HR(+)/HER2(-) subtypes.

Distribution, driving forces, and risk assessment of 2-MIB and its producer in a drinking water source-oriented shallow lake.

Freshwater blooms of harmful cyanobacteria in drinking water source-oriented shallow lakes affect public health and ecosystem services worldwide. Therefore, identifying 2-methylisoborneol (2-MIB)-producing cyanobacteria and predicting the risks of 2-MIB are critical for managing 2-MIB-infected water sources. Previous studies on the potential producers and risks of 2-MIB have focused on reservoirs or have been limited by the ecosystems of phytoplankton-dominated areas. We investigated the producers, distribution, and occurrence of 2-MIB in East Taihu Lake-a drinking water source-oriented shallow lake with macrophyte- and phytoplankton-dominated areas-from August 2020 to November 2021. We observed that Pseudanabaena sp. produces 2-MIB in this lake, as determined by the maximum correlation coefficient (R = 0.71, p < 0.001), maximum detection rate, and minimum false positive/negative ratio exhibited by this genus. Extreme odor events occurred in this lake during late summer and early autumn in 2021, with the mean 2-MIB concentration increasing to 727 ± 426 ng/L and 369 ± 176 ng/L in August and September, respectively. Moreover, the macrophyte-dominated area, particularly the wetland area, exhibited a significant decrease (p < 0.01) in bloom intensity and 2-MIB production during these extreme odor events. Pseudanabaena sp. outbreak was likely owing to eutrophication, seasonal gradients, and macrophyte reduction, considering that temporal trends were consistent with high water temperature, high total phosphorus levels, and low-light conditions. Moreover, 2-MIB production was sensitive to short-term hydrometeorological processes, with high water levels and radiant intensity enhancing 2-MIB production. The risk assessment results showed that the probability of 2-MIB concentration exceeding the odor threshold (10 ng/L) is up to 90% when the cell density of Pseudanabaena sp. reaches 1.8 × 107 cell/L; this risk is reduced to 50 and 25% at densities of < 3.8 × 105 cell/L and 5.6 × 104 cell/L, respectively. Our findings support calls for shallow lake management efforts to maintain a macrophyte-dominated state and control odorous cyanobacteria growth.

Intergenerational Integration in Community Building to Improve the Mental Health of Residents-A Case Study of Public Space.

This study defined intergenerational integration in communities at a theoretical level and verified whether a series of measures could facilitate negotiation and communication between community residents and other stakeholders to generate a positive and healthy community environment and gradually improve intergroup relations. Specifically, we applied community psychology and used Hongqiao New Village in Shanghai, China, as a research site to explore intergenerational conflict in public community spaces. The research was divided into two stages: an input stage and an output stage. In the input stage, participatory research and tea parties were used to deeply explore residents' public space requirements. In the output stage, we tested the validity of the theory by using the Intergenerational Attitude Scale to investigate whether the intergenerational relationships were changed by the co-creation intervention. The results showed that the intervention caused a decrease in the incidence of conflict between residents using the square and caused some children to join the older groups in their activities. We thus propose a theoretical system model of intergenerational integration strategies that incorporates elements of integration, disagreement, and synergy in intergenerational interactions. Overall, this paper provides new ideas for building a community environment that supports mental health and improves intergenerational relationships and social well-being.

Percutaneous endoscopic lumbar discectomy in lumbar disc herniation with posterior ring apophysis fracture: A case report in a 15-year-old child.

RATIONALE: Lumbar disc herniation (LDH) with posterior ring apophysis fracture (PRAF) is rather rare in children, and in all age-stratified LDH patients, the incidence of RAF was 5.3% to 7.5%. Interestingly, the incidence of LDH with RAF in children (15%-32%) is several times higher than in adults, the mis-diagnosis of which may lead to delayed treatment. PATIENT CONCERNS: Here, we report a 15-year-old schoolboy who suffered from sudden low back pain and radiating pain in both lower limbs after sport activities. Symptoms persisted after 3 months of conservative treatment. Computer radiography and magnetic resonance imaging indicated central disc herniation with PRAF at L4-5. DIAGNOSIS: LDH with PRAF. INTERVENTIONS: The herniated disc and epiphyseal fragments were successfully excised by the percutaneous endoscopic lumbar discectomy minimal-invasive technique. OUTCOMES: Surgery was successful. Symptoms were immediately relieved postoperatively with a wound of only about 7.0 mm. Discharged on the next day. No perioperative complications occurred. Moreover, the imaging and clinical outcomes were also more satisfactory during the post-operative 15 months outpatient follow-up. LESSONS: Pediatric LDH with PRAF is extremely uncommon, and there is a lack of training among physicians for such cases, which may lead to delayed diagnosis and treatment. Once a diagnosis for LDH with PRAF is established, percutaneous endoscopic lumbar discectomy is a safe and effective minimally invasive treatment to be considered, and we hope that this technique can provide more assistance in the future.

Genetic risk modifies the effect of long-term fine particulate matter exposure on coronary artery disease.

BACKGROUND: Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood. METHODS: A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM2.5 exposures were assessed by adopting satellite-based PM2.5 estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM2.5 exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM2.5 exposure and CAD risk. RESULTS: During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM2.5 exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05-1.54) and 1.95 (1.57-2.42) among intermediate and high PM2.5 exposure groups compared to low PM2.5 exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18-1.66) and 133% (HR: 2.33, 95%CI: 1.94-2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM2.5 exposure, those with high genetic risk and high PM2.5 exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13-6.11). We observed significant multiplicative (P < 0.001) and additive interaction [relative excess risk due to interaction (95%CI): 2.75 (1.32-4.20); attributable proportion due to interaction (95%CI): 0.56 (0.42-0.70)] between genetic risk and PM2.5 exposure on CAD. CONCLUSION: This study provided evidence that long-term PM2.5 exposure might increase CAD risk, especially among people at high genetic risk. Our findings highlighted the importance of taking strategies on air quality improvement to cardiovascular disease prevention.

Blockchain based energy efficient multi-tasking optimistic scenario for mobile edge computing.

Mobile edge computational power faces the difficulty of balancing the energy consumption of many devices and workloads as science and technology advance. Most related research focuses on exploiting edge server computing performance to reduce mobile device energy consumption and task execution time during task processing. Existing research, however, shows that there is no adequate answer to the energy consumption balances between multi-device and multitasking. The present edge computing system model has been updated to address this energy consumption balance problem. We present a blockchain-based analytical method for the energy utilization balance optimization problem of multi-mobile devices and multitasking and an optimistic scenario on this foundation. An investigation of the corresponding approximation ratio is performed. Compared to the total energy demand optimization method and the random algorithm, many simulation studies have been carried out. Compared to the random process, the testing findings demonstrate that the suggested greedy algorithm can improve average performance by 66.59 percent in terms of energy balance. Furthermore, when the minimum transmission power of the mobile device is between five and six dBm, the greedy algorithm nearly achieves the best solution when compared to the brute force technique under the classical task topology.

Incorporating the Co-Creation Method into Social Innovation Design to Promote Intergenerational Integration: A Case Study of a Public Square.

With the COVID-19 pandemic sweeping the world, there is an increased focus on intergenerational relationships, community mental health issues, and well-being in community contexts. This paper assesses the effectiveness of a co-creation approach for intergenerational integration at the theoretical level. The study used a collaborative co-creation design method in the community design process to explore whether the participation of community residents of all ages in addressing community issues promoted communication and alleviated stereotyping between the various generations. This study was conducted in Shanghai's Hongqiao New Village square, where we conducted participatory research and co-creation workshops in response to the demand for the use of the public space as a location for social interactions. The results showed that intervention in community creation through collaborative design is conducive to promoting friendly relations among different age groups, forming a sense of social security and thus enhancing social well-being. Finally, this paper combines practical cases and theoretical models of collaborative co-creative design approaches to promote the intergenerational integration of communities and is summarized from the input and output parts as well as the influencing factors and constraints of the collaborative co-creative. In addition, it provides new ideas on how to improve intergenerational relationships and form a positive and sustainable community mental health environment in the future.

Li-doped calcium phosphate cement for accelerated bone regeneration of osteoporotic bone defect.

Osteoporotic fractures seriously endanger the elderly quality of life, especially postmenopausal women. Currently, calcium phosphate cement (CPC) is one of the materials used for the treatment of osteoporotic fractures. This study intends to investigate the biological effects of lithium (Li)-doped CPC. Li was dissolved into ultrapure water as curing solution to prepare CPC@Li composite material. Li did not affect the morphology of CPC. CPC@Li composite showed a sustained release of Li in 14 days. Compared with CPC, CPC@Li promoted the adhesion, proliferation, and osteogenic differentiation of rat bone marrow stem cells. The result of femur implantation in an osteoporosis mouse model showed that a larger amount of new bone was formed surrounding the CPC@Li implant and closely to the implant surface, indicating favorable osteogenesis and osteointegration capabilities. Li-doped CPC is promising to be used in clinic for its enhanced bone regeneration ability.

Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation.

Non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancer cases, calls for better therapy. Yi-Fei-San-Jie-pill (YFSJ), a well-applicated traditional Chinese medicine formula, was reported to be effective in the treatment of NSCLC. However, its anti-tumor mechanism still needs to be fully elucidated. Herein, a reliable preclinical orthotopic but not subcutaneous model of NSCLC in mice was established to evaluate the anti-cancer properties and further validate the mechanisms of YFSJ. A bioinformatic analysis was executed to identify the potential targets and key pathways of YFSJ on NSCLC. In detail, the anti-tumor effect of YFSJ and the autophagy inhibitor 3-MA was evaluated according to the tumor fluorescence value and comparison of different groups' survival times. As a result, YFSJ markedly decreased tumor size and prolonged survival time in contrast with those in the orthotopic model group (p < 0.05), and it also significantly regulated the protein expression levels of apoptosis- and autophagy-related proteins. In conclusion, this study provides convincing evidence that YFSJ could inhibit the growth of tumors and prolong the survival time of tumor-bearing mice based on the NSCLC orthotopic model, and its anti-tumor effect was closely associated with the promotion of apoptosis and interference of autophagy coupled with regulation of immune infiltration.

Tryptophan-rich diet ameliorates chronic unpredictable mild stress induced depression- and anxiety-like behavior in mice: The potential involvement of gut-brain axis.

Tryptophan, an essential amino acid, has been reported that it has the potential to regulate depression-like behavior. Meanwhile, Chronic stress-induced depression also has a close relationship with gut microbiota structure and composition. In the current research, we demonstrated that a tryptophan-rich diet (0.6% tryptophan w/w) significantly attenuated depression- and anxiety-like behaviors in a chronic unpredictable mild stress (CUMS)-treated mouse model. Tryptophan supplementation improved neuroinflammation, increased expression of BDNF, and improved mitochondrial energy metabolism in the brain of CUMS-treated mice. Besides, CUMS also enhanced the kynurenine pathway, but repressed the serotonin pathway and indole pathway of tryptophan metabolism, leading to a decrease in 5-HT and indole in serum, whereas tryptophan supplementation might shift the tryptophan metabolism more toward the serotonin pathway in CUMS-treated mice. The gut microbiome was restructured by increasing the relative abundance of Lachnospiracea, Clostridium, Lactobacillus, Bifidobacterium in tryptophan-treated depressive mice. Moreover, tryptophan administration inhibited stress-induced gut barrier damage and decreased inflammatory responses in the colon. Together, our study purports the gut-brain axis as a mechanism for the potential of tryptophan to improve depression and anxiety-related behavior.

Identification of CD4+ Conventional T Cells-Related lncRNA Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Breast Cancer.

Background: Breast cancer (BC) is one of the most common malignancies in women, and long non-coding RNAs (lncRNAs) are key regulators of its development. T cells can recognize and kill cancer cells, and CD4+ T conventional (Tconv) cells are the main orchestrators of cancer immune function. However, research on CD4+ Tconv-related lncRNAs (CD4TLAs) prognostic signature in patients with BC is still lacking. Method: A TCGA database and a GEO database were used to collect the BC patients. Through LASSO Cox regression analysis CD4TLAs-related prognostic models were further constructed, and risk scores (RS) were generated and developed a nomogram based on CD4TLAs. The accuracy of this model was validated in randomized cohorts and different clinical subgroups. Gene set enrichment analysis (GSEA) was used to explore potential signature-based functions. The role of RS has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. Result: A prognostic model based on 16 CD4TLAs was identified. High-RS was significantly associated with a poorer prognosis. RS was shown to be an independent prognostic indicator in BC patients. The low-RS group had a significant expression of immune infiltrating cells and significantly enriched immune-related functional pathways. In addition, the results of immunotherapy prediction indicated that patients with low-RS were more sensitive to immunotherapy. Conclusions: Our signature has potential predictive value for BC prognosis and immunotherapy response. The findings of this work have greatly increased our understanding of CD4TLA in BC.

Oral vitamin D3 supplementation for femtosecond LASIK-associated dry eye vitamin D for LASIK dry eye syndrome.

PURPOSE: To assess the effect of oral vitamin D3 supplementation in dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). SETTING: Liuzhou Worker's Hospital. DESIGN: This prospective study included 90 patients selected between January and December in 2019, who underwent FS-LASIK operation in our hospital and had obvious symptoms indicating dry eyes 1 month after operation. The subjects were randomly divided into two groups: The experimental group (n = 45) received vitamin D3 2000 IU/D continuously for 12 weeks; the control group (n = 45) did not take vitamin D3 orally. Ocular surface disease index (OSDI), Tear breakup time (TBUT) and Schirmer's test I were evaluated premedication and 1,3,6 months after treatment. Serum vitamin D3 level and the mean concentration of cytokine IL-6, IL-17, IL-23 in t ears were also measured. RESULTS: One month after treatment, the mean OSDI score of the experimental group (11.67 ± 8.53) was significantly lower than that of the control group (23.82 ± 13.22) (P = 0.007). TBUT (10.71 ± 1.02 s) and Schirmer I (9.36 ± 0.40 mm) of the experimental group were higher than those of the control group (7.49 ± 1.29 s and 7.51 ± 0.44 mm). The OSDI (10.25 ± 5.49) was significantly lower than those of the control group(20.22 ± 6.23) and TBUT (10.75 ± 1.09 s) and Schirmer I test value (11.34 ± 0.39 mm) of the experimental group were significantly higher than those of the control group (8.36 ± 1.23, 8.12 ± 0.50) at 3 months after treatment. There were significant differences in OSDI, TBUT (P < 0.05) and Schirmer I test value between the two groups at 6 months after treatment. Serum vitamin D3 level was negatively correlated with OSDI score (r = - 0.90; P = 0.00) and positively correlated with Schirmer I test (r = 0.88; P = 0.00), TBUT score (r = 0.89; P = 0.00) and TMH (r = 0.80; P = 0.00). IL-17 level was shown to be significantly correlated with TBUT(r = - 0.25, P = 0.014) and Schirmer I test (r = - 0.21, P = 0.018). IL-6 level was significantly correlated with OSDI (R = 0.18, P = 0.020) and TBUT (R = 0.20, P = 0.019).

Impaired metabolism of oligodendrocyte progenitor cells and axons in demyelinated lesion and in the aged CNS.

The key pathology of multiple sclerosis (MS) comprises demyelination, axonal damage, and neuronal loss, and when MS develops into the progressive phase it is essentially untreatable. Identifying new targets in both axons and oligodendrocyte progenitor cells (OPCs) and rejuvenating the aged OPCs holds promise for this unmet medical need. We summarize here the recent evidence showing that mitochondria in both axons and OPCs are impaired, and lipid metabolism of OPCs within demyelinated lesion and in the aged CNS is disturbed. Given that emerging evidence shows that rewiring cellular metabolism regulates stem cell aging, to protect axons from degeneration and promote differentiation of OPCs, we propose that restoring the impaired metabolism of both OPCs and axons in the aged CNS in a synergistic way could be a promising strategy to enhance remyelination in the aged CNS, leading to novel drug-based approaches to treat the progressive phase of MS.

Maternal exposures to fine and ultrafine particles and the risk of preterm birth from a retrospective study in Beijing, China.

Maternal exposure to fine particulate matter (PM2.5) has been associated with increased risk of preterm birth (PTB), but evidence on particles in smaller sizes and PTB risk remains limited. In this retrospective analysis, we included birth records of 24,001 singleton live births from Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. Concurrently, number concentrations of size-fractioned particles in size ranges of 5-560 nm (PNC5-560) and mass concentrations of PM2.5, black carbon (BC) and gaseous pollutants were measured from a fixed-location monitoring station in central Haidian District. Logistic regression models were used to estimate the odds ratio (OR) of air pollutants on PTB risk after controlling for temperature, relative humidity, and individual covariates (e.g., maternal age, ethnicity, gravidity, parity, gestational weight gain, fetal gender, the year and season of conception). Positive matrix factorization models were then used to apportion the sources of PNC5-560. Among the 1062 (4.4%) PTBs, increased PTB risk was observed during the third trimester of pregnancy per 10 µg/m3 increase in PM2.5 [OR = 1.92; 95% Confidence Interval (95% CI): 1.76, 2.09], per 1000 particles/cm3 increase in PNC25-100 (OR = 1.09; 95% CI: 1.03, 1.15) and PNC100-560 (OR = 1.22; 95% CI: 1.05, 1.42). Among the identified sources of PNC5-560, emissions from gasoline and diesel vehicles were significantly associated with increased PTB risk, with ORs of 1.14 (95% CI: 1.01, 1.29) and 1.11 (95% CI: 1.04, 1.18), respectively. Exposures to other traffic-related air pollutants, such as BC and nitrogen dioxide (NO2) were also significantly associated with increased PTB risk. Our findings highlight the importance of traffic emission reduction in urban areas.