ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Neural loops are formed by interconnections between neurons through synaptic structures,which are the basic units of information transmission and processing in the brain and play an important role in the regulation of neural functions.After stroke,neural connections between the infarct and peri-infarct regions and the remote area are damaged,resulting in patients being at risk of neurological dysfunction or even disability.However,with advances in detection technology,an increasing number of studies are demonstrating that patients with stroke can undergo some functional recovery during the chronic phase,possibly via a mechanism related to the re-establishment of synaptic connections and neural circuits.Therefore,the development of specific technology to identify and manipulate neuronal activity patterns,as well as the use of high-resolution temporal and spatial imaging strategies to decipher these neurological processes,will allow us to understand the whole-brain network dynamics of stroke recovery and the mechanisms by which neural loop reestablishment occurs.Furthermore,we may be able to neurobiologically comprehend the closed-loop mechanisms that underlie the development of stroke pathology and their relationship to behavioral outcomes.Current technologies used for studying neural circuits include optogenetics,chemical genetics,in vivo calcium imaging,and functional magnetic resonance imaging.This article introduces the working principles of these four major technologies and focuses on summarizing the result of their respective application in resolving neural remodeling after stroke.We briefly analyze the application scenarios,advantages and disadvantages,and future development trends of each technique.This paper will help clinical and basic researchers to use these technologies to discover new therapeutic strategies and evaluate the effectiveness of rehabilitation strategies.

Objective:To investigate the application value of computer-assisted preoperative planning (CAPP) in the treatment of AO/OTA type-C distal femoral fractures.Methods:A retrospective analysis was conducted on 150 patients with AO/OTA type-C distal femur fractures from January 2010 to December 2021 using the less invasive stabilization system-distal femur (LISS-DF). Patients were divided into a non-CAPP group and a CAPP group based on whether computer-assisted preoperative planning was utilized. The non-CAPP group included 81 patients (56 males, 25 females) with an age range of 39 to 67 years (mean 54.9±5.8 years), consisting of 22 type-C1 fractures, 35 type-C2 fractures, and 24 type-C3 fractures. The CAPP group comprised 69 patients (50 males, 19 females) with an age range of 45 to 63 years (mean 53.9±4.6 years), including 18 type-C1 fractures, 28 type-C2 fractures, and 23 type-C3 fractures. The study recorded the time of preoperative planning and compared the surgical duration, intraoperative blood loss, times of fluoroscopy intraoperatively, and hospital stay length between the two groups. At the last follow-up, knee function was evaluated using the Hospital for Special Surgery (HSS) knee score and pain was assessed using the visual analogue scale (VAS).Results:The preoperative planning time of CAPP was 22.5±3.4 min (range, 17-31 min). There were statistically significant differences between non-CAPP group and CAPP group in terms of surgical duration (non-CAPP, 110.9±7.7 min; CAPP, 94.4±6.3 min), intraoperative blood loss (non-CAPP, 299.3±34.2 ml; CAPP, 224.1±22.0 ml), times of fluoroscopy intraoperatively (non-CAPP, 11.3±3.1; CAPP, 6.7±2.2), and hospital stay length (non-CAPP, 12.8±3.2 d; CAPP, 6.4±1.9 d) ( P<0.001). All patients were followed up, with the CAPP group having a follow-up duration of 17.7±3.3 months and the non-CAPP group having 18.1±3.7 months. Both groups of patients achieved clinical healing of fractures. The healing time for fractures in the CAPP group and the non-CAPP group were 13.9±1.1 weeks and 14.0±1.3 weeks, respectively, with no statistically significant difference ( t=0.699, P=0.490). At the last follow-up, the average HSS score and VAS score of the patients in the CAPP group were 86.6±3.4 points and 0.9±0.4 points, which were both better than those of the non-CAPP group 79.2±5.1 points and 1.3±0.5 points ( P<0.001). No patients in either group experienced complications related to delayed fracture healing, nonunion, or internal fixation failure. Conclusion:When using LISS -DF steel plate to treat complex distal femoral fractures, CAPP can assist the operator in efficiently and accurately completing preoperative design. Compared with traditional preoperative planning, it can reduce surgical time, surgical trauma, and achieve more satisfactory postoperative outcomes.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective:To investigate the role of long non-coding RNA nuclear paraspeckle assembly transcript 1 (Neat1) in pyroptosis of ultraviolet B (UVB)-induced human lens epithelial cells (LECs) and to explore the possible mechanism.Methods:The human lens epithelial cell line HLE-B3 was cultured in vitro, and cells at log phase were exposed to ultraviolet B for 0, 2, 4 and 8 hours, respectively.The expression of cysteine aspartic acid-specific protease-1 (caspase-1), a protein related to pyroptosis, was detected by Western blot.The relative expression level of Neat1 in cells after different irradiation durations was determined by real-time quantitative PCR.Cell viability was determined by the cell counting kit-8 (CCK-8) method to screen the optimal irradiation duration for UVB-induced LECs pyroptosis, which was finally determined to be 4 hours.HLE-B3 cells were divided into negative siRNA transfection group, siRNA Neat1 transfection group, negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group, and were transfected with corresponding reagents for 24 hours.The negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group were irradiated with UVB for 4 hours after transfection.The cell viability was detected by the CCK-8 method.The pyroptosis rate was detected by flow cytometry.The expression levels of caspase-1, gasdermin D (GSDMD) and nod-like receptor protein 3 (NLRP3) proteins were detected by Western blot.The concentration of interleukin (IL)-1β was detected by enzyme-linked immunosorbent assay (ELISA). Ultrastructural changes in HLE-B3 cells were observed under a transmission electron microscope. Results:The grayscale of caspase-1 protein bands increased with the extension of irradiation duration.The relative expression levels of caspase-1 protein at 0, 2, 4 and 8 hours of irradiation were 0.05±0.01, 0.25±0.07, 0.51±0.04 and 0.74±0.02, respectively, with a statistically significant overall difference ( F=168.223, P<0.001), and significant differences were found in paired comparisons (all at P<0.05). With prolonged irradiation, the relative expression level of Neat1 mRNA increased and the cell viability decreased, with statistically significant differences in paired comparisons (all at P<0.05). Compared with negative siRNA transfection group, the cell viability was increased in siRNA Neat1 transfection group and decreased in negative siRNA transfection+ irradiation group, with statistically significant differences (both at P<0.01). Compared with negative siRNA transfection+ irradiation group, the cell viability was increased in siRNA Neat1 transfection+ irradiation group, showing a statistically significant difference ( P<0.05). The pyroptosis rate was significantly lower in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group than in negative siRNA transfection+ irradiation group, and the differences were statistically significant (both at P<0.01). The relative expression levels of caspase-1, NLRP3 and GSDMD proteins in negative siRNA transfection+ irradiation group were higher than those in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group and the differences were statistically significant (all at P<0.01). The concentration of IL-1β was significantly higher in negative siRNA transfection+ irradiation group than in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group, and the differences were statistically significant (all at P<0.05). Cell swelling, formed cell membrane pores, vacuolated cells and fuzzy mitochondrial cristae were seen in negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group by transmission electron microscopy.Compared with negative siRNA transfection+ irradiation group, slighter cell swelling, fewer cell membrane pores and lighter mitochondrial swelling were seen in siRNA Neat1 transfection+ irradiation group. Conclusions:Neat1 is involved in human LECs pyroptosis induced by UVB through the classic pyroptosis pathway mediated by caspase-1.Knockdown of Neat1 can inhibit the pyroptosis of human LECs.

Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.

Objective:To provide reference for clinical diagnosis and treatment of hepatic cystic echinococcosis by analyzing the clinical characteristics of these patients.Methods:Clinical data of 15 patients with hepatic cystic echinococcosis hospitalized in the Second Hospital of Lanzhou University from April 22, 2019 to March 5, 2022 were collected. The general data, clinical manifestations, abdominal imaging results, treatment and outcome of the included patients were retrospectively analyzed.Results:The age of 15 patients with hepatic cystic echinococcosis ranged from 39 to 78 years, with a median age of 51 years. Among the 15 patients, 12 were farmers, two were freelance workers, and one was unknown. Eleven patients presented with abdominal pain and fatigue, one patient presented with obstructive jaundice, and three patients whom were found by physical examination did not complain of obvious discomfort. Echinococcoid cysts were located at the right lobe of the liver in eight patients, at the left lobe of the liver in five patients, and with multiple lesions in the left and right lobes of the liver in two patients. Two patients received conservative therapy. All the 13 patients who received surgical treatment recovered without complications, such as biliary fistula and subphrenic infection. The clinical symptoms including abdominal pain and fatigue were relieved significantly after surgery. The hospital stay were four to 23 days. All patients were administrated with albendazole (400 mg once daily).Conclusions:Hepatic cystic echinococcosis is more common in the right lobe of the liver, with atypical clinical symptoms. Preoperative imaging diagnosis and postoperative pathological examination are necessary for diagnosis. Surgery is the most effective treatment at present, and albendazole should be taken regularly in all patients.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.