Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Objective:To observe the effects of adipose-derived stem cells(ADSC)combined with acellular scaffold(AS)on the ultrastructure of dorsal root ganglion and the protein and mRNA expression levels of ciliary neurotrophic factor(CNTF),Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phosphorylated STAT3(p-STAT3)in the rats with sciatic nerve injury(SNI),and to clarify the protective effect of ADSC combined with AS on dorsal root ganglion in the SNI rats and its possible mechanism.Methods:The rat ADSCs were isolated and cultured and their multidirectional differentiation potential was detected.The AS of rats was prepared,and ADSCs were injected into the AS to construct tissue-engineered nerve.A total of 36 rats were randomly divided into control group,model group,AS group,and ADSC+AS group.The rats in control group were routinely fed,and the rats in other groups were used to establish the SNI models by resecting 10 mm of right sciatic nerve.The rats in model group received no further treatment,while the rats in AS group and ADSC+AS group were bridged with AS and the constructed tissue-engineered nerve at the two ends of the injured nerve,respectively.At 6 weeks after surgery,transmission electron microscope was used to observe the ultrastructure of dorsal root ganglion of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of CNTF,p-JAK2,and p-STAT3 in dorsal root ganglion of the rats;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of CNTF,JAK2,and STAT3 in dorsal root ganglion of the rats in various groups.Results:After 7 d of primary ADSC culture,a large number of large and long spindle-shaped cells were observed under the inverted microscope,arranged in clusters or whirlpools;red lipid droplets were observed with oil red O staining under microscope,and calcified nodules were observed with Alizarin red staining under microscope,indicating that the isolated and cultured cells had multidirectional differentiation ability.Compared with normal nerve tissue,the level of DNA in AS of rats was significantly decreased(P<0.05).Compared with control group,the nuclear membrane of dorsal root ganglion cells in model group was uneven and serrated,the number of organelles in the cytoplasm was decreased,mitochondria were swollen with broken or missing cristae and unclear structure;the CNTF protein and mRNA expression levels were significantly decreased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly increased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly increased(P<0.01).Compared with model group,the serrated change of nuclear membrane of the dorsal root ganglion cells in AS group was significantly alleviated,the number of organelles in the cytoplasm was increased,and mitochondrial swelling was reduced;in ADSC+AS group,the nuclear membrane of dorsal root ganglion cells tended to be intact,the number of organelles was increased,and mitochondrial swelling and vacuolization were significantly reduced;the CNTF protein and mRNA expression levels in the dorsal root ganglion in AS group and ADSC+AS group were significantly increased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Compared with AS group,the CNTF protein and mRNA expression levels in ADSC+AS group were significantly increased(P<0.05 or P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Conclusion:The application of ADSC combined with AS can improve the ultrastructure of dorsal root ganglion in the SNI rats,and the mechanism may be related to the increased CNTF expression and decreased activation of the JAK2/STAT3 signaling pathway in the dorsal root ganglion by ADSC combined with AS application.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis