Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

Retinoid X receptor gamma dictates the activation threshold of group 2 innate lymphoid cells and limits type 2 inflammation in the small intestine.

Group 2 innate lymphoid cells (ILC2s) are crucial in promoting type 2 inflammation that contributes to both anti-parasite immunity and allergic diseases. However, the molecular checkpoints in ILC2s that determine whether to immediately launch a proinflammatory response are unknown. Here, we found that retinoid X receptor gamma (Rxrg) was highly expressed in small intestinal ILC2s and rapidly suppressed by alarmin cytokines. Genetic deletion of Rxrg did not impact ILC2 development but facilitated ILC2 responses and the tissue inflammation induced by alarmins. Mechanistically, RXRγ maintained the expression of its target genes that support intracellular cholesterol efflux, which in turn reduce ILC2 proliferation. Furthermore, RXRγ expression prevented ILC2 response to mild stimulations, including low doses of alarmin cytokine and mechanical skin injury. Together, we propose that RXRγ expression and its mediated lipid metabolic states function as a cell-intrinsic checkpoint that confers the threshold of ILC2 activation in the small intestine.

Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.

Irg1 regulates bone homeostasis via regulating the Grk5 expression.

We have previously demonstrated that itaconic acid can regulate osteoclast differentiation in vitro and in vivo, thereby affecting the progression of osteoporosis. The role of Irg1 as itaconic acid catalytic enzyme in bone homeostasis has not been clearly elucidated. Here, we detected enhanced the osteoclast differentiation in Irg1-deficiency BMMs, along with the expression of genes associated with osteoclastogenesis. Irg1 knockout promoted the expression of Nfatc1 and F-actin ring formation, with the inhibited production of itaconate. RNA-seq analysis was carried out and we proved that Grk5 expression was increased the most. Inhibition of Grk5 attenuated the effect of Irg1 in the osteoclastogenesis. However, micro-CT analysis showed no significant difference of bone trabecular structure in Irg1 knockout mice. Moreover, we observed no significant difference of osteoclasts numbers in the femur of Irg1 knockout mice in vivo. And similar bone formation was detected between the Irg1 knockout and WT mice, indicating that irg1 had slight effect on the bone homeostasis under physiological conditions. Surprising, we detected higher level of inflammatory factors in the bone tissues of Irg1 knockout mice. Above all, we for the first time demonstrated that Irg1 knockout promoted the osteoclastogenesis via regulating the Grk5 signaling. Regulation of irg1-Grk5 axis could be effective in treating human diseases under pathological situations in the future.

Off-label Use of Mycophenolate Mofetil in Immunoglobulin A Nephropathy: A Systematic Review and Meta-analysis.

INTRODUCTION: Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety. METHODS: We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause. RESULTS: Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (RR, 0.32; 95%CI, 0.13 to 0.77), reducing proteinuria (RR, 1.41; 95%CI, 1.22 to 1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14 to 0.72). No significant differences were detected in the incidence of ESRD (RR: 0.87, 95% CI: 0.38 to 2.03), or progression of chronic kidney disease (RR, 1.01; 95%CI, 0.22 to 4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95%CI, 1.21 to 4.00). CONCLUSION: MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still needs need further cross-regional and cross-ethnical verification.

Cdc42GAP deficiency contributes to the Alzheimer's disease phenotype.

Alzheimer's disease, the most common cause of dementia, is a chronic degenerative disease with typical pathological features of extracellular senile plaques and intracellular neurofibrillary tangles and a significant decrease in the density of neuronal dendritic spines. Cdc42 is a member of the small G protein family that plays an important role in regulating synaptic plasticity and is regulated by Cdc42GAP, which switches Cdc42 from active GTP-bound to inactive GDP-bound states regulating downstream pathways via effector proteins. However, few studies have focused on Cdc42 in the progression of Alzheimer's disease. In a heterozygous Cdc42GAP mouse model that exhibited elevated Cdc42-GTPase activity accompanied by increased Cdc42-PAK1-cofilin signalling, we found impairments in cognitive behaviours, neuron senescence, synaptic loss with depolymerization of F-actin and the pathological phenotypes of Alzheimer's disease, including phosphorylated tau (p-T231, AT8), along with increased soluble and insoluble Aß1-42 and Aß1-40, which are consistent with typical Alzheimer's disease mice. Interestingly, these impairments increased significantly with age. Furthermore, the results of quantitative phosphoproteomic analysis of the hippocampus of 11-month-old GAP mice suggested that Cdc42GAP deficiency induces and accelerates Alzheimer's disease-like phenotypes through activation of GSK-3ß by dephosphorylation at Ser9, Ser389 and/or phosphorylation at Tyr216. In addition, overexpression of dominant-negative Cdc42 in the primary hippocampal and cortical neurons of heterozygous Cdc42GAP mice reversed synaptic loss and tau hyperphosphorylation. Importantly, the Cdc42 signalling pathway, Aß1-42, Aß1-40 and GSK-3ß activity were increased in the cortical sections of Alzheimer's disease patients compared with those in healthy controls. Together, these data indicated that Cdc42GAP is involved in regulating Alzheimer's disease-like phenotypes such as cognitive deficits, dendritic spine loss, phosphorylated tau (p-T231, AT8) and increased soluble and insoluble Aß1-42 and Aß1-40, possibly through the activation of GSK-3ß, and these impairments increased significantly with age. Thus, we provide the first evidence that Cdc42 is involved in the progression of Alzheimer's disease-like phenotypes, which may provide new targets for Alzheimer's disease treatment.

Associations of prenatal and concurrent exposure to phenols mixture with anthropometric measures and blood pressure during childhood: A time-varying mixture approach.

BACKGROUND: Environmental phenols were recognized as endocrine disrupting chemicals (EDCs). However, their impact on childhood anthropometric measures and blood pressure (BP) is still inconclusive. Limited studies have simultaneously considered prenatal and childhood exposures in analyzing mixtures of phenols. OBJECTIVE: We investigated the relationships between combined prenatal and childhood exposures (two periodic exposures) to phenol mixtures and anthropometric measure and BP, to further identify the vulnerable periods of phenol exposure and to explore the important individual contribution of each phenol. METHODS: We analyzed 434 mother-child dyads from the Sheyang Mini Birth Cohort Study (SMBCS). The urinary concentrations of 11 phenolic compounds were measured using gas chromatography tandem mass spectrometry. Generalized linear regression models (GLMs) and hierarchical Bayesian Kernel Machine Regression (hBKMR) were used to examine the effects of individual phenolic compounds at each period and of two periodic exposures. RESULTS: In the single-chemical analysis, prenatal or childhood exposure to specific phenols, especially Benzopheone-3 (BP3), 4-tert-Octylphenol (4-tOP), and Benzyl paraben (BePB) were associated with BMI z-scores (BAZ), Waist-to-height ratio (WHtR), and BP. In the hBKMR models, two periodic exposures to phenol mixtures had a U-shaped association with WHtR, primarily driven by childhood BePB exposure. Moreover, among the phenol mixtures analysis, childhood 4-tOP exposure was identified as the primary contributor to the positive association with diastolic BP. Concurrent exposure to phenol mixtures resulted in greater susceptibility. CONCLUSIONS: We found that prenatal and childhood exposure to phenol mixtures might influence childhood obesity and elevate blood pressure levels. Concurrent exposure to 4-tOP may be the primary driver of the positive associations with BP.

Sex-specific associations of per- and polyfluoroalkyl substances with brain-derived neurotrophic factors (BDNF) in cord serum.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration. OBJECTIVE: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum. METHODS: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis. RESULTS: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 µg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (ß: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches. CONCLUSIONS: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific.

Identification of a novel transcriptional regulator, CorR, for copper stress response in Edwardsiella piscicida.

Copper plays a vital role in the host-pathogen interface, potentially making components of the bacterial copper response suitable targets for the development of innovative antimicrobial strategies. The anti-copper arsenal of intracellular pathogens has expanded as an adaptation to survive copper toxicity in order to escape intracellular killing by the host immune system. Herein, we employed transposon insertion sequencing to investigate the genetic mechanisms underlying the survival of Edwardsiella piscicida under copper stress. A novel transcriptional regulator, ETAE_2324 (named CorR), was identified to participate in the response to copper ions by controlling the expression of copA, the core component of cytoplasmic copper homeostasis. Furthermore, CorR regulated the expression of virulent determinant eseB, influencing the in vivo colonization of E. piscicida. Collectively, our results contribute to the comprehension of the underlying mechanism of the adaption of intracellular pathogens to copper stress during bacterial infections.IMPORTANCECopper ions play a pivotal role in the interaction between bacteria and the host during infection. The host's innate immune system employs copper ions for their bactericidal properties, thereby making bacterial copper tolerance a crucial determinant of virulence. Edwardsiella piscicida, a significant marine pathogen, has caused substantial losses in the global aquaculture industry. To comprehensively investigate how E. piscicida responds to copper stress, we utilized transposon insertion sequencing to explore genes associated with copper tolerance in culture media containing different concentrations of copper ions. A novel transcriptional regulator, CorR, was identified to respond to copper ions and regulates the expression of crucial components of copper homeostasis CopA, along with the essential virulence factor EseB. These findings offer valuable insights into the underlying mechanisms that govern bacterial copper tolerance and present novel perspectives for the development of vaccines and therapeutic strategies targeting E. piscicida.

Ab initio molecular dynamics calculations on electron ionization induced fragmentations of C4F7N and C5F10O for understanding their decompositions under discharge conditions.

C4F7N and C5F10O are the most promising SF6 alternatives as eco-friendly insulating gaseous mediums in electrical engineering. It is necessary to clarify their electrical stability and decomposition mechanisms. In this work, we first introduced our experimental results for decomposition products of C4F7N/CO2 and C5F10O/synthetic air mixtures under partial discharge and spark discharge conditions. Then, we performed ab initio molecular dynamics (AIMD) simulations on the typical decomposition products. The simulations were performed under standard electron impact mass spectrometry (EI-MS); thus, the statistical results of the mass spectra were compared with those of the experimentally obtained standard mass spectra from the NIST database. The AIMD simulation method in simulating the electron-induced ionization process was verified and found to be reliable. Finally, the calculations were also performed for C4F7N and C5F10O with incident electron energies of 20 eV and 70 eV, respectively. The dominant pathway for both gases is the formation of CF3+ with the fracture of the C-C bond. The AIMD simulation is able to predict the decomposition channels after electron-impact ionization without any preconceived knowledge of fragmentation pathways, which provides a novel insight into understanding the decomposition mechanisms of C4F7N and C5F10O under different discharge conditions with different energies.

Interactions between quorum sensing/quorum quenching and virulence genes may affect coral health by regulating symbiotic bacterial community.

Quorum sensing (QS) and quorum quenching (QQ) are two antagonistic processes that may regulate the composition, function and structure of bacterial community. In coral holobiont, autoinducers signaling mediate the communication pathways between interspecies and intraspecies bacteria, which regulate the expression of the virulence factors that can damage host health. However, under environmental stressors, the interaction between the QS/QQ gene and virulence factors and their role in the bacterial communities and coral bleaching is still not fully clear. To address this question, here, metagenomics method was used to examine the profile of QS/QQ and virulence genes from a deeply sequenced microbial database, obtained from three bleached and non-bleached corals species. The prediction of bacterial genes of bleached samples involved in functional metabolic pathways were remarkably decreased, and the bacterial community structure on bleached samples was significantly different compared to non-bleached samples. The distribution and significant difference in QS/QQ and virulence genes were also carried out. We found that Proteobacteria was dominant bacteria among all samples, and AI-1 system is widespread within this group of bacteria. The identified specific genes consistently exhibited a trend of increased pathogenicity in bleached corals relative to non-bleached corals. The abundance of pathogenicity-associated QS genes, including bapA, pfoA and dgcB genes, were significantly increased in bleached corals and can encode the protein of biofilm formation and the membrane damaging toxins promoting pathogenic adhesion and infection. Similarly, the virulence genes, such as superoxide dismutase (Mn-SOD gene), metalloproteinase (yme1, yydH and zmpB), glycosidases (malE, malF, malG, and malK) and LodAB (lodB) genes significantly increased. Conversely, QQ genes that inhibit QS activity and virulence factors to defense the pathogens, including blpA, lsrK, amiE, aprE and gmuG showed a significant decrease in bleached groups. Furthermore, the significant correlations were found among virulence, QS/QQ genes, and coral associated bacterial community, and the virulence genes interact with key QS/QQ genes, directly or indirectly influence symbiotic bacterial communities homeostasis, thereby impacting coral health. It suggested that the functional and structural divergence in the symbiont bacteria may be partially attribute to the interplay, involving interactions among the host, bacterial communication signal systems, and bacterial virulence factors. In conclusion, these data helped to reveal the characteristic behavior of coral symbiotic bacteria, and facilitated a better understanding of bleaching mechanism from a chemical ecological perspective.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Long bone shaft metastasis: a comparative study between cement filling and intercalary prosthesis.

BACKGROUND: Metastatic bone lesions in the extremities can cause severe pain and pathological fractures, significantly affecting patients' quality of life. Timely intervention and effective management of long bone metastases can positively influence patient outcomes, including survival rates and subsequent treatment options. OBJECTIVE: The objective of this study is to compare the efficacy and associated complications of two surgical reconstruction techniques and propose a more effective limb reconstruction approach for long bone metastases. METHODS: A retrospective study was conducted on 28 patients with complete clinical data who underwent a surgical procedure for long bone metastases of the extremities in our department between January 2017 and June 2022. The patients were divided into two groups based on their surgical methods. In group 1, the affected bones were curetted and filled with cement, then secured with plates or intramedullary nails. In group 2, the affected bone segments were completely removed and replaced with custom intercalary prostheses. Various factors, including general patient information, surgical details, surgical effectiveness, and common complications, were compared and analyzed. RESULTS: There were no significant differences in general patient information between the two groups, including age, gender, surgical site, and primary tumor type. The operative times were 115.37 min for group 1 and 108.90 min for group 2, respectively (p > 0.05). However, intraoperative blood loss differed significantly between the groups, with 769 ml in group 1 and 521 ml in group 2 (p < 0.05). The postoperative MSTS scores were 91% for group 1 and 92% for group 2 (p > 0.05). Postoperative complications included two cases of internal fixation failure and three cases of tumor recurrence in group 1, resulting in a 33% incidence rate, while group 2 experienced a 15% incidence rate with two cases of internal fixation failure. CONCLUSION: The results of this study suggest that both surgical techniques are effective for the treatment of long bone metastases of the extremities. However, the custom intercalary prostheses technique in group 2 showed a lower incidence of complications and less intraoperative blood loss. Therefore, it may be a more effective limb reconstruction approach for long bone metastases. Further studies with larger sample sizes are needed to confirm these findings.

The pedicled sartorius flap and mesh (PSM) technique vs no reconstruction in repairing the defect after type III pelvic bone tumor resection: a retrospective study.

BACKGROUND: Type III pelvic bone tumor resections are often accompanied by postoperative complications. In order to reduce complications, we developed a novel pedicled sartorius flap and mesh (PSM) technique to reconstruct the pelvic ring defect. In this study, we evaluated the efficacy and risks of this PSM technique in type III pelvic bone tumor resections by comparing outcomes between patients that underwent PSM reconstruction and patients that did not receive any reconstruction. METHODS: We retrospectively reviewed a consecutive set of patients that underwent type III pelvic bone tumor surgeries in our center from January 2020 to January 2021 with either PSM reconstruction (designated as the PSM group) or without any reconstruction (designated as the control group). General information such as age, gender, tumor type, tumor size, and surgical-related information such as duration of surgery, blood loss, and the surgical margins was collected. Outcome data recorded included wound complications such as infection and dehiscence, local recurrence, and Musculoskeletal Tumor Society (MSTS) scores for postoperative functional evaluation. Statistical analysis between both groups was performed with GraphPad Prism v7. RESULTS: A total of 20 patients were included in this study (PSM group n = 12, control group n = 8). While no herniation was found in the PSM group, it occurred in 6 of 8 cases in the control group. The control group showed a significantly higher rate of bacterial infection (p = 0.03) and wound dehiscence (p = 0.02) but lower MSTS scores (p < 0.05) compared to the PSM group. CONCLUSIONS: The use of the PSM technique can significantly reduce postoperative complication rates and enhance postoperative function following type III pelvic bone tumor resection.

Sex-specific associations of maternal and childhood urinary arsenic levels with emotional problems among 6-year-age children: Evidence from a longitudinal cohort study in China.

BACKGROUND: Arsenic exposure has been linked to neurobehavior development disorders among children in cross-sectional studies, but there is little information on the effects of prenatal and childhood arsenic exposure on childhood behavior problem, especially emotional problems. OBJECTIVE: To explore the relationship between prenatal and childhood arsenic exposure and behavior problems among six-year-old children. METHODS: 389 mother-child pairs from a longitudinal birth cohort were enrolled in the study. The concentrations of arsenic in maternal and 6-year-old children's urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Neurobehavioral development in 6-year-old children was assessed by Child Behavior Checklist (CBCL). Generalized linear regression models were used to relate arsenic exposure to the score of different domains in CBCL. RESULTS: The median concentrations of maternal and 6-year-old children's urinary arsenic were 22.22 and 33.86 µg/L, respectively. After adjusting for potential covariates, natural logarithm transformed concurrent urinary arsenic levels were significantly associated with scores of anxious and depressed problems in 6-year-old girls (ß = 0.71, 95% CI: 0.12-1.31, p = 0.018). Furthermore, in terms of the trajectory of arsenic exposure, compared with the "consistently low" group, the "low to high" group (ß = 2.73, 95% CI: -3.99 to 9.45, p = 0.425) had a greater effect on total score of CBCL than "high to low" group (ß = -0.93, 95% CI: -7.22 to 5.36, p = 0.771) in girls, although insignificant. CONCLUSIONS: Our results suggested that concurrent arsenic exposure might have an adverse effect of emotional status in girls. Further studies are needed to verify the findings and explore the mechanisms of the sex-specific association.

Associations between Physical Activity Trajectories and Incident Hypertension.

Purpose: We aimed to characterize physical activity (PA) trajectories across adulthood and to estimate their association with incident hypertension risk. Methods: Data were obtained from the China Health and Nutrition Survey (CHNS) conducted during 2004-2011. Group-based trajectory modeling (GBTM) was used to identify distinct groups of PA trajectories. The Cox proportional hazards model was used to investigate the association. Results: A total of 11,162 participants whose PA was repeatedly estimated by self-report from questionnaires two to four times in the CHNS were included in our study. During the 5.4 years of follow-up, 3824 incident hypertension cases were identified. Five distinct PA trajectories were identified in men: light and slight decline, light and gradual decline then sharp rise, light to medium-heavy then decline, medium-heavy and gradual decline, and heavy and sharp decline. Two distinct PA trajectories were identified in women: light and stable, and medium and gradual decline. The PA trajectory of medium-heavy and gradual decline was significantly associated with decreased risk of hypertension in men, with the hazard ratios and 95% confidence intervals (CI) being 0.80 (0.63, 0.99), 0.74 (0.59, 0.93), 0.76 (0.60, 0.96), and 0.70 (0.55, 0.88) in models 1-4, respectively. Conclusions: Our study identified five distinct long-term PA trajectories in men and two distinct trajectories in women. The PA trajectory of medium-heavy PA in early adulthood followed by gradual decline was found to be significantly associated with a decreased risk of hypertension in later life in men.

Experience in utilizing a novel 3D digital model with CT and MRI fusion data in sarcoma evaluation and surgical planning.

OBJECTIVE: To assess sarcoma margins with more accuracy and aid surgical planning, we constructed three-dimensional (3D) digital models with computed tomography(CT) and magnetic resonance imaging (MRI) image fusion data and validated the preciseness of the models by comparing them with 3D models constructed with CT only data. MATERIALS AND METHODS: We retrospectively reviewed a consecutive set of patients treated in our center who were preoperatively evaluated with the fusion image model. Models based on fusion images or CT-only data were constructed. Volumes of both tumors were calculated and the tumors were overlapped to see the location of differences between the two models. RESULTS: A consecutive 12 cases (4 male vs. 8 female) were included in this study. Most of the tumors were located in the pelvic bone or spine. The volume of the two tumor models was different and the differences were mainly in the peripheral region of the tumor. CONCLUSION: CT and MRI fusion image 3D models are more accurate than models with CT-only data and can be very helpful in preoperative planning of sarcoma patients.

Study of ultrasound-guided ropivacaine combined with butorphanol continuous paravertebral block to prevent pain syndrome by evaluating ccl2 gene expression after radical mastectomy.

This study aimed to investigate the clinical effect of ultrasound-guided ropivacaine combined with butorphanol continuous paravertebral block in preventing postoperative pain syndrome of breast cancer. For this purpose, 100 women treated for breast cancer from April 2018 to July 2019 were enrolled as research objects. Surgical procedures included local sentinel lymph node biopsy, mastectomy, sentinel lymph node biopsy for mastectomy, modified radical mastectomy, and implantation. The selected patients were randomly divided into two groups: control group (routine operation anesthesia; n = 50) and observation group (ultrasound-guided thoracic paravertebral block before induction of ropivacaine+butorphanol anesthesia; n = 50). The Real-time PCR technique was performed to evaluate CCL2 gene expression. VAS scores were recorded during the postoperative period. Compared with the control group, the observation group had lower VAS scores at six h, 24h, and 48h (P<0.05). The pain effect of the observation group was less than that of the control group. The observation group had better analgesic effects after anesthesia. The observation group had a lower incidence of pain syndrome at the 6th, 8th, and 12th months (P<0.05), and the incidence of pain syndrome in the two groups decreased with the extension of time. The observation group had lower levels of related factors (P<0.05), and the observation group had lower traumatic stress responses. The protein expression of IL-6, IL-17, and CRP in the observation group was lower than that in the control group (P<0.05). The results of CCL2 gene expression also showed that gene expression in the control group increased significantly (P=0.0047). Since the expression of this gene is one of the factors that stimulate pain signals in the body, the method used in the present study was able to reduce the amount of pain significantly. Therefore, the combination of ropivacaine combined with butorphanol ultrasound-assisted paravertebral block can reduce the intensity of postoperative pain in patients with breast cancer surgery, decrease the incidence of pain syndrome, and increase pain tolerance.

Intercomparison of equivalent black carbon (eBC) and elemental carbon (EC) concentrations with three-year continuous measurement in Beijing, China.

Due to the lack of black carbon (BC) measurement data in some cases, elemental carbon (EC) is often used as a surrogate of BC, with a simple assumption that they are interchangeable. Such assumption will inevitably lead to uncertainties in radiative forcing estimation and health impact assessment. In order to quantitatively and systematically evaluate the relationship between BC and EC as well as factors responsible for their difference, 3-year collocated equivalent BC (eBC) and EC measurements with 1-h resolution were performed in Beijing, China continuously from 2016 to 2019. EBC concentration was measured by the multi-wavelength aethalometer (AE-33) based on optical analysis, while EC concentration was determined by semi-continuous OC/EC analyzer with thermal-optical method. The results showed that around 90% of eBC concentration was higher than that of EC, with average difference between eBC and EC as 1.21 µg m-3 (accounting for 33% of average eBC in Beijing). EBC and EC concentrations exhibited strong correlation (r = 0.90) during the whole study period, but the slopes (or eBC/EC ratio) and correlation coefficients varied across seasons (spring: 1.67 and 0.94; summer: 0.91 and 0.65; fall: 1.15 and 0.88; winter: 1.09 and 0.91, respectively). Based on the information from shell/core ratios by Single Particle Soot Photometer (SP2), source apportionment results by positive matrix factorization model, and chemical composition of PM2.5, the differences between eBC and EC concentrations were found to be primarily related to BC aging process and secondary components as evidenced by strong positive correlation with secondary species (e.g., secondary organic carbon and nitrate). This study provided seasonal specific conversion factors of eBC and EC in Beijing and helpful reference for other areas, which will contribute new knowledge of carbonaceous aerosol and reduce uncertainty in assessing future climate change and health studies of BC.

Malting barley carbon dots-mediated oxidative stress promotes insulin resistance in mice via NF-κB pathway and MAPK cascade.

BACKGROUND: Food-borne carbon dots (CDs) are widely generated during food processing and are inevitably ingested by humans causing toxicity. However, the toxic effects of food-borne CDs on the blood glucose metabolism are unknown. RESULTS: In this study, we brewed beer via a representative strategy and extracted the melting-barley CDs (MBCDs) to explore the toxic effects on blood glucose in mice. We found the accumulation of fluorescent labeled MBCDs in various organs and oral administration of MBCDs can cause visceral toxicity, manifested as liver damage. Mice were orally administered MBCDs (5 and 25 mg/kg) for 16 weeks, and increased levels of fasting blood glucose were observed in both MBCDs-treated groups. Transcriptomic analyses revealed that MBCDs activate oxidative stress, inflammatory responses, the MAPK cascade, and PI3K/Akt signaling in mice livers. Mechanistically, MBCDs exposure-induced reactive oxygen species (ROS) overproduction activates the nuclear factor-κB (NF-κB) signaling pathway and MAPK cascade, thereby promoting phosphorylated insulin receptor substrate (IRS)-1 at Ser307 and inducing insulin resistance (IR). Meanwhile, the IR promoted gluconeogenesis, which enhanced MBCDs-induced hyperglycemia of mice. Importantly, inhibition of the ROS significantly attenuated the MBCDs-induced inflammatory response and MAPK cascade, thereby alleviating IR and hyperglycemia in mice. CONCLUSION: In summary, this study revealed that MBCDs promote ROS overproduction and thus induced IR, resulting in imbalance of glucose homeostasis in mice. More importantly, this study was further assessed to reveal an imperative emphasis on the reevaluation of dietary and environmental CDs exposure, and has important implications for T2DM prevention research.