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BACKGROUND/OBJECTIVES: Coffee is one of the most popularly consumed beverages worldwide. Many epidemiological studies have investigated the association between coffee consumption and lung cancer risk, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to examine this association and derive a more precise estimation. SUBJECTS/METHODS: The Cochrane library, PubMed and Embase databases were searched to identify studies published through Mar 2015 that met the predetermined inclusion criterion. Seventeen studies (5 cohort and 12 case-control studies) involving 12 276 cases and 102 516 controls were included. RESULTS: The summary odds ratio (OR) of lung cancer was 1.17 (95% confidence interval (CI): 1.03-1.33) for coffee drinkers compared with nondrinkers and 1.31 (95% CI: 1.11-1.55) for the highest category of coffee consumption compared with the lowest category. Compared with nondrinkers, the pooled ORs for lung cancer were 1.10 (95% CI: 0.92-1.31) for [less than or equal to] 1 cup per day, 1.10 (95% CI: 0.93-1.30) for 2-3 cups per day and 1.20 (95% CI: 1.02-1.39) for ≥ 3 cups per day. Further analysis showed that the ORs for hospital-based case-control studies, population-based case-control studies and prospective cohort studies were 1.36 (95% CI: 1.10-1.69), 0.99 (95% CI: 0.77-1.28) and 1.59 (95% CI: 1.26-2.00), respectively. Significant associations for high coffee intake with increased risk of lung cancer were observed in men (OR = 1.41 95% CI: 1.21-1.63), but not in women (OR = 1.16, 95% CI: 0.86-1.56), in American (OR = 1.34 95% CI: 1.08-1.65) and Asian populations (OR = 1.49 95% CI: 1.28-1.74), but not in European populations (OR = 1.12, 95% CI: 0. 74-1.67), and in smokers (OR = 1.24, 95% CI: 1.00-1.54), but not in nonsmokers (OR = 0.85, 95% CI: 0.64-1.11). Particularly over the last 5 years, studies have consistently indicated that lung cancer risk is significantly increased by 47% in the population with the highest category intake of coffee compared with that with the lowest category intake (OR =1.47, 95% CI: 1.21-1.79). CONCLUSION: The present study suggested that coffee intake was associated with an increased risk of lung cancer. European Journal of Clinical Nutrition (2016) 70, 199-206; doi: 10.1038/ejcn.2015.96; published online 17 June 2015, INTRODUCTION Lung cancer is one of the most prevalent malignancies and is the leading cause of cancer death in the United States, in both men and women. (1) The incidence [...]

This study aimed to analyse the treatment and outcomes of traumatic hip dislocation (THD) in children. Clinical data of children with THD were collected at our clinical centre from 1 June 2012 to 1 January 2023. Demographic data, injury mechanism, type of dislocation, combined injuries, reduction time, reduction method, and radiographs were analysed. The Merle d'Aubigné-Postel hip score was used to evaluate hip function and complications at the final follow-up. A total of 19 children with THD were enrolled, including 12 male and seven female patients, with an average age of 8.28 ± 0.99 years. Posterior dislocation was the main type of dislocation (89.47%). Fifteen patients (78.95%) had experienced high-energy injuries and traffic accidents were the main causes of injury (47.37%). Closed reduction was performed as soon as possible, and open reduction was performed if necessary. The hip scores of 18 patients (94.74%) were excellent. One patient had osteonecrosis of the femoral head, with a hip function score of 10 (moderate). High-energy injuries, such as traffic accidents, have gradually become the main cause of injury. The prognosis for THD in children is generally good., (© 2024. The Author(s).)

A large number of economic forests, especially apple orchards (AOs) in the Loess Plateau region of China, have been planted to develop the local economy and increase the income of farmers. The two main constraints preventing AOs on the Loess Plateau from developing sustainably and producing a high and steady yield are soil moisture content (SMC) and soil organic carbon (SOC). Nevertheless, little is currently known about the contributions of roots to these changes in the soil profile and the temporal modes of the SMC-SOC coupled effects. In our research, we analyzed the dynamic changes in SMC and SOC in AOs of various years in northern Shaanxi Province, as well as the coupled relationship between the two, and attempted to describe the function of roots in these changes. Research have shown: (1) As the age of the AOs increased, the SMC continued to decline throughout the 0-500 cm profile, especially at depths of 100-500 cm. SMC depletion mainly occurred in AOs aged 20 years (30.02%/year) and 30 years (31.18%/year). (2) Compared with abandoned land (AL), all the AOs except for the 6-year-old AO showed a carbon sequestration effect, and the carbon sequestration effect increased with age. The carbon sequestration rate of the 12-year-old AO was the highest and then decreased with age. Both surface and deeper soils showed better carbon sequestration, with a large amount of SOC being sequestered in deeper soil layers (> 100 cm). (3) The coupled effects of SMC and SOC varied with age and depth. The SMC in the deeper layers was significantly negatively correlated with SOC. Root dry weight density (RDWD) was significantly negatively correlated with SMC and significantly positively correlated with SOC. Path analysis suggested that SMC directly affects SOC at different soil depths, and regulates SOC by affecting RDWD, but these effects are significantly different at different depths. Therefore, we propose that management of AO should focus on the moisture deficit and carbon sequestration capabilities of deeper soils to ensure the sustainability of water use in AOs and the stability of agricultural carbon sequestration on the Loess Plateau., (© 2024. The Author(s).)

The optimal treatment for acute intussusception has not yet been defined. In this study, we explored whether employing a liberal laparoscopic intervention for intussusception could lead to favorable outcomes. We performed a historical control analysis to evaluate the outcomes associated with this liberal surgical management protocol. This liberal surgical management protocol were revised to incorporate a new protocol centered around the laparoscopic approach. In some cases of acute intussusception, liberal laparoscopic exploration and intervention were undertaken without initial hydrostatic or pneumatic reduction. During the study interval, a retrospective review was conducted on a total of 3086 patients. These were categorized into two groups: 1338 cases before May 2019 (pre-protocol group) and 1748 cases after May 2019 (post-protocol group). Surgical intervention rates in the pre-protoco and post-protocol period were 10.2% and 27.4% respectively (odds ratio [OR] = 0.30 [95% CI 0.25-0.37]; p < 0.001). No significant differences were observed in baseline clinical characteristics or demographic features between the two groups. The duration from admission to operation was longer for the pre-protocol group (p = 0.008) than for the post-protocol group. The post-protocol group demonstrated decreases in both intestinal resection (OR = 1.50 [95% CI 0.96-2.35]; p = 0.048) and total recurrent events (OR = 1.27 [95% CI 1.04-1.55]; p = 0.012) compared to the pre-protocol group. Liberal laparoscopic intervention for intussusception may effectively reduce the risk of intestinal resection and total recurrent events, thereby exhibiting promising outcomes for patients with intussusception., (© 2024. The Author(s).)

Lung cancer is the leading cause of cancer-related mortality worldwide. CNOT3, a subunit of the CCR4-NOT complex, has recently been suggested to be overexpressed in lung cancer and involved in tumor malignancy. However, its precise role and the underlying mechanisms still need to be fully revealed. In the present study, we found in lung cancer cells the expression of CNOT3 could be regulated by EGFR signaling pathway and c-Jun, a transcription factor downstream of EGFR, transcriptionally regulated its expression. Interestingly, CNOT3 could inversely regulate the expression of c-Jun via modulating its translation. Thus, a feedback loop existed between c-Jun and CNOT3. CNOT3 reduction post EGFR blockade facilitated the drug-induced cell death, and simultaneously inhibited cell proliferation via impacting TSC1/mTOR axis. Whereas, further up-regulation of the CNOT3 expression was observed in gefitinib-resistant cells, which dampened gefitinib sensitivity. Mechanically, the elevation of CNOT3 was induced by the bypass activation of HER2/c-Jun signaling. Depleting CNOT3 in vitro and in vivo sensitized the drug-resistant cells to gefitinib treatment and inhibited metastatic progression. These results give novel insights into the role of CNOT3 in lung cancer malignancy and provide a theoretical basis for the development of therapeutic strategies to solve acquired resistance to EGFR-TKIs., (© 2023. The Author(s).)

Severe injury occurs in the lung after acute spinal cord injury (ASCI) and autophagy is inhibited. However, rapamycin-activated autophagy's role and mechanism in lung injury development after ASCI is unknown. Preventing lung injury after ASCI by regulating autophagy is currently a valuable and unknown area. Herein, we aimed to investigate the effect and possible mechanism of rapamycin-activated autophagy on lung damage post-ASCI. An experimental animal study of rapamycin's effect and mechanism on lung damage after ASCI. We randomly divided 144 female wild-type Sprague-Dawley rats into a vehicle sham group (n = 36), a vehicle injury group (n = 36), a rapamycin sham group (n = 36), and a rapamycin injury group (n = 36). The spine was injured at the tenth thoracic vertebra using Allen's method. At 12, 24, 48, and 72 h after surgery, the rats were killed humanely. Lung damage was evaluated via pulmonary gross anatomy, lung pathology, and apoptosis assessment. Autophagy induction was assessed according to LC3, RAB7, and Beclin 1 levels. ULK-1, ULK-1 Ser555, ULK-1 Ser757, AMPK α and AMPK β1/2 were used to investigate the potential mechanism. After rapamycin pretreatment, the lung showed no obvious damage (e.g., cell death, inflammatory exudation, hemorrhage, and pulmonary congestion) at 12 h and 48 h after injury and Beclin1, LC3 and RAB7 levels increased. After rapamycin pretreatment, ULK-1, ULK-1 Ser555, and ULK-1 Ser757 levels increased at 12 h and 48 h after injury compared with the vehicle group, but they decreased at 12 h after injury compared with the rapamycin sham group. After rapamycin pretreatment, AMPKα levels did not change significantly before and after injury; however, at 48 h after injury, its level was elevated significantly compared with that in the vehicle group. Rapamycin can prevent lung injury after ASCI, possibly via upregulation of autophagy through the AMPK-mTORC1-ULK1 regulatory axis., (© 2023. The Author(s).)

Fracture nonunion is a common and challenging complication. Although direct current stimulation has been suggested to promote fracture healing, differences in cell density near the positive and negative electrodes have been reported during direct current stimulation. This study aimed to explore the effects of these differences on osteoblast proliferation and fracture healing. MC3T3-E1 cells were stimulated by positive and negative charges to observe cell proliferation, apoptosis, and osteogenic factor expression in vitro, while positive and negative charges were connected to the Kirschner wires of the fractures in an in vivo double-toe fracture model in New Zealand white rabbits and fracture healing was assessed in digital radiography (DR) examinations performed on days 1, 15, 30. Bone tissue samples of all rabbits were analysed histologically after the last examination. The results showed that in comparison with the control group, after DC stimulation, the number of cells near the positive electrode decreased significantly (P &lt; 0.05), apoptosis increased (P &lt; 0.05), the expression of osteocalcin, osteoblast-specific genes, and osteonectin decreased significantly near the positive electrode (P &lt; 0.05) and increased significantly at the negative electrode (P &lt; 0.05). The fracture at the positive electrode junction of New Zealand white rabbits did not heal. Histomorphological analysis showed more bone trabeculae and calcified bone in the bone tissue sections of the control group and the negative electrode group than in the positive electrode group. The bone trabeculae were thick and showed good connections. However, positive charge inhibited osteoblast proliferation and a positive charge at fracture sites did not favour fracture healing. Thus, a positive charge near the fracture site may be a reason for fracture nonunion., (© 2022. The Author(s).)

Though the great success of paclitaxel, the variable response of patients to the drug limits its clinical utility and the precise mechanisms underlying the variable response to paclitaxel remain largely unknown. This study aims to verify the role and the underlying mechanisms of CD147 in paclitaxel resistance. Immunostaining was used to analyze human non-small-cell lung cancer (NSCLC) and ovarian cancer tissues. RNA-sequencing was used to identify downstream effectors. Annexin V-FITC/propidium iodide and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect apoptosis. Co-immunoprecipitation (Co-IP), fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) were performed to determine protein interactions. Fluorescence recovery after photobleaching (FRAP) was performed to measure the speed of microtubule turnover. Xenograft tumor model was established to evaluate sensitivity of cancer cells to paclitaxel in vivo. In vitro and in vivo assays showed that silencing CD147 sensitized the cancer cells to paclitaxel treatment. CD147 protected cancer cells from paclitaxel-induced caspase-3 mediated apoptosis regardless of p53 status. Truncation analysis showed that the intracellular domain of CD147 (CD147 ICD ) was indispensable for CD147-regulated sensitivity to paclitaxel. Via screening the interacting proteins of CD147 ICD , Ran binding protein 1 (RanBP1) was identified to interact with CD147 ICD via its C-terminal tail. Furthermore, we showed that RanBP1 mediated CD147-regulated microtubule stability and dynamics as well as response to paclitaxel treatment. These results demonstrated that CD147 regulated paclitaxel response by interacting with the C-terminal tail of RanBP1 and targeting CD147 may be a promising strategy for preventing paclitaxel resistant., (© 2021. The Author(s).)

Major gaps in understanding the molecular mechanisms of colorectal cancer (CRC) progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders. Trefoil factor 3 (TFF3) has been reported to be involved in CRC progression and intestinal mucosal repair; however, how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood. Here, we found that the upregulated TFF3 in CRC predicted a worse overall survival rate. TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis. CD147, a membrane protein, was identified as a binding partner for TFF3. Via binding to CD147, TFF3 enhanced CD147-CD44s interaction, resulting in signal transducer and activator of transcription 3 (STAT3) activation and prostaglandin G/H synthase 2 (PTGS2) expression, which were indispensable for TFF3-induced migration, proliferation, and invasion. PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype (PTGER4) and contributed to TFF3-stimulated CRC progression. Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression. The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor. Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice. Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression, which widens and deepens the understanding of the molecular function of trefoil factors., (© 2021. The Author(s).)

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [ 18 F]-Fluoro-2-deoxy-2-D-glucose ( 18 F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18 F-FDG accumulation and 18 F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18 F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18 F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18 F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18 F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

Traumatic injury to the spinal cord causes permanent loss of function and major personal, social, and economic problems. Cell-based delivery strategies is a promising approach for treating spinal cord injury (SCI). However, the inhospitable microenvironment in the injured spinal cord results in poor cell survival and uncontrolled differentiation of the transplanted stem cells. The combination of a scaffold with cells has been developed with a tendency for achieving greater survival and integration with the host tissue. We investigated the effect of Matrigel combined with neural stem cells (NSCs) in vitro and in vivo. We compared the effect of different types of scaffold on the survival and differentiation of brain-derived NSCs in an in vitro culture. Subsequently, NSCs were transplanted subcutaneously into nude mice to detect graft survival and differentiation in vivo. Finally, phosphate-buffered saline (PBS), Matrigel alone, or Matrigel seeded with NSCs was injected into 48 subacute, clinically relevant rat models of SCI (16 rats per group). Matrigel supported cell survival and differentiation efficiently in vitro and in vivo. SCI rats transplanted with NSCs in Matrigel showed improved behavioral recovery and neuronal and reactive astrocyte marker expression levels compared to PBS- or Matrigel-transplanted rats. Functional repair and neuronal and reactive astrocyte marker expression was slightly improved in the Matrigel-alone group relative to the PBS group, but not statistically significantly. These data suggest that Matrigel is a promising scaffold material for cell transplantation to the injured spinal cord.

Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter process was performed to prioritize rare variants of potential functional significance. In all cases where parental testing was accessible, Sanger sequencing confirmed the variants and determined the parental origin. In 15% of patients (n = 10/68), we identified nine de novo pathogenic variants, and one assumed de novo pathogenic variant in the following genes: CDKL5 (n = 2), STXBP1 (n = 2), SCN1A (n = 3), KCNQ2 (n = 2), SCN8A (n = 1), four of the variants are novel variants. In 4% patients (n = 3/68), we identified three likely pathogenic variants; two assumed de novo and one X-linked in the following genes: SCN1A (n = 2) and ARX (n = 1), two of these variants are novel. Variants were assumed de novo when parental testing was not available. Our findings were first reported in Han Chinese patients with unexplained EIEE, enriching the EIEE mutation spectrum bank.