Objective:To investigate the protection effect of a new 360-degree radiation protection and position fixation device on the pelvic cavity during chest CT examination.Methods:Three shielding methods were applied to the pelvic cavity of the standard simu-lated human model,i.e.,no shielding(group A),traditional 180-degree front protection with a lead square towel(group B),and 360-degree protection with a new protection device(group C).Philips IQon Spectral CT was used to perform chest CT scan at a tube voltage of 80 kVp,100 kVp,and 120 kVp,respectively,and the cumulative radiation doses from the front,side,and back of the pelvic cavity were measured and analyzed statistically.Results:Compared with groups A and B,group C had significantly lower cumulative radiation doses of the front,side,and back of the pelvic cavity in the simulated human model(all P<0.05);at the tube voltages of 80,100,and 120 kVp,the cumulative dose of the pelvic cavity in group C was reduced by 85%,84%,and 67%,respectively,compared with that in group B,and was reduced by 88%,87%,and 76%,respectively,compared with that in group A.Compared with group A,group B had significant reductions in the radiation doses of the side and back of the pelvic cavity(P<0.05)and a significantly higher radiation dose of the front of the pelvic cavity,which was increased by 19%,23%,and 10%,respectively,at the tube voltages of 80,100,and 120 kVp,and there were significant differences in all tube voltage conditions(P<0.05)except under the tube voltage condition of 120 kVp(P=0.190).In addition,after the application of the device for protection,the reduction rate of pelvic radiation dose under the tube voltages of 80 and 100 kVp was higher than that under the tube voltage of 120 kVp.Conclusion:The new 360-degree radiation protection and position fixation device can significantly reduce the cumulative radiation dose of pelvic organs during chest CT scan,and it holds promise for clinical application due to its characteristics of conve-nient wearing and fixed patient position.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To evaluate the therapeutic value of radiotherapy in combined immunotherapy and chemotherapy as first-line treatment for patients with oligometastatic non-small cell lung cancer (NSCLC).Methods:A retrospective analysis was conducted on data from 195 NSCLC patients who lacked epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations and were treated at the Anyang Tumor Hospital and the Fourth Hospital of Hebei Medical University from January 2019 to December 2021. These patients consisted of 166 male and 29 female cases, aged from 28 to 85 years, with an average age of (61.4 ± 9.3) years. These patients were divided into two groups, with each group receiving the radiotherapy and combined immunotherapy and chemotherapy (the radiotherapy and combination group, n = 60) and combined immunotherapy and chemotherapy only (the combination group, n = 135). Then, propensity score matching (PSM) was performed to analyze the differences in prognosis between both groups before and after PSM, as well as the short-term efficacy and adverse reactions after PSM. Results:For the 195 NSCLC patients, the median follow-up time was 31.8 months, with median overall survival (OS) and median progression-free survival (PFS) recorded at 23.8 months and 9.2 months, respectively. The radiotherapy and combination group exhibited enhanced 1-, 2-, and 3-year survival rates of 78.5%, 55.9%, and 45.1%, respectively, significantly higher than the combination group (48.3%, 35.6%, and 26.6%, respectively, χ2 = 14.65, P < 0.001). Similarly, the radiotherapy and combination group displayed 1-, 2-, and 3-year PFS rates of 51.9%, 29.5%, and 22.7%, respectively, exceeding those of the combination group (30.0%, 24.5%, and 16.9%, respectively, χ2=6.09, P=0.014). After PSM, the radiotherapy and combination group manifested an objective response rate (ORR) of 60.0% (33/55) and a disease control rate (DCR) of 89.1% (49/55), which were 16.4% (9/55) and 56.4% (31/55), respectively for the combination group. These results suggested that the radiotherapy and combination group demonstrated significantly higher ORR and DCR ( χ2 = 22.18, 14.85, P<0.001). After PSM, the radiotherapy and combination group yielded 1-, 2-, and 3-year survival rates of 70.9%, 52.3%, and 41.9%, respectively, significantly than the combination group (43.6%, 29.8%, and 27.1%, respectively, χ2=8.95, P=0.003). The radiotherapy and combination group exhibited 1-, 2-, and 3-year PFS rates of 47.3%, 27.3%, and 18.7%, respectively, significantly higher than the combination group (23.6%, 17.6%, and 15.4%, respectively, χ2 = 6.71, P = 0.010). Multivariate Cox regression analysis revealed that independent factors affecting OS included clinical stage, treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.88, 2.11, 0.23, 1.79, P < 0.05). Similarly, independent factors affecting PFS consisted of treatment regimen, number of immunotherapy cycles, and treatment efficacy ( HR = 1.62, 0.37, 3.42, P <0.05). There were no statistical differences in the incidence of grade ≥ 2 bone marrow suppression (18.2% vs. 12.7%) and grade ≥ 2 pneumonia (21.8% vs. 14.5%) between both groups ( P>0.05). Conclusions:Introducing radiotherapy into combined immunotherapy and chemotherapy as first-line treatment for oligometastatic NSCLC can optimize both local and systemic disease control and significantly improve patient prognosis without increasing treatment-related adverse reactions.

Objective:To explore the feasibility of using a simplified multiple sleep latency test (MSLT) for the diagnosis of narcolepsy type 1.Methods:Data from 158 patients with narcolepsy type 1 and 58 patients with non-type 1 narcolepsy who underwent overnight video-polysomnography (V-PSG) and MSLT in the Sleep Center, Department of Neurology, Xijing Hospital, Air Force Military Medical University from March 2019 to April 2024 were retrospectively collected. By reducing the number of naps in the MSLT, the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT was evaluated using the receiver operating characteristic (ROC) curve. The DeLong test was used to compare whether there was a statistically significant difference between the simplified MSLT and the standard 5-nap MSLT. Cohen′s Kappa statistical analysis was performed to compare the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT.Results:The age of the 216 patients who were ultimately enrolled was 17 (13, 30) years, including 152 male patients (70.4%). The Cohen′s Kappa between the simplified 3-nap MSLT and the standard 5-nap MSLT was 0.875, which was 0.903 between the simplified 4-nap MSLT and the standard 5-nap MSLT (Bonferroni-corrected, both P0.001), indicating high and statistically significant agreement for both simplified protocols with the standard test. However, the DeLong test revealed that the area under the curve of the standard 5-nap MSLT (0.900, 95% CI 0.863-0.938) differed significantly from that of the simplified 3-nap MSLT (0.860, 95% CI 0.817-0.904; P0.05), whereas no significant difference was observed between the standard 5-nap MSLT and the simplified 4-nap MSLT (0.876, 95% CI 0.834-0.918; P0.05). Consequently, performing only the first 4 naps was sufficient for diagnosing narcolepsy type 1. Conclusion:The simplified 4-nap MSLT, specifically the first to fourth naps, may be used for the diagnosis of narcolepsy type 1.

Objective To investigate the mechanism of modified Guizhi Fuling Pills in treating diabetic kidney disease(DKD)through autophagy regulation based on network pharmacology and experimental validation.Methods Active components and action targets of modified Guizhi Fuling Pills were screened via the TCMSP database.DKD-related autophagy targets were obtained from GeneCards,TTD,DrugBank and PharmGKB.A protein-protein interaction network was constructed using STRING,followed by GO functional and KEGG pathway enrichment analyses via DAVID.Molecular docking of key components and core targets was performed using AutoDock Tools 1.5.7.DKD model rats were prepared.The rats were randomly divided into normal group,model group,valsartan group(50 mg/kg),and modified Guizhi Fuling Pills low-,medium-and high-dosage group(9.9,19.8 and 39.6 g/kg).After 8-week interventions,body mass and water intake were recorded;fasting blood glucose,24 h urinary total protein(24 hUTP),urinary albumin-to-creatinine ratio(UACR)were monitored.Renal histopathology was evaluated via HE and Masson staining.Western blot was used to detect protein expressions of AMPK/FOXO1 pathway(p-AMPK,AMPK,FOXO1)and autophagy markers(Beclin-1,p62),while quantitative real-time PCR was used to assess AMPK and FOXO1 mRNA expressions.Results A total of 146 active components of Guizhi Fuling Pills and 33 main targets for treating DKD were screened,with the core targets including FOXO1,BCL2,TP53 and PTEN.KEGG pathway enrichment analysis suggested that AMPK/FOXO1 signaling pathway,AGE-RAGE and insulin signaling pathways may play a core regulatory role.Guizhi Fuling Pills could significantly reduce the body mass of DKD rats,reduce water intake,decrease renal index,decrease fasting blood glucose,24 hUTP and UACR(P<0.05,P<0.01),improve renal tissue pathology,increase AMPK,FOXO1,Beclin-1 protein expressions and AMPK,FOXO1 mRNA expressions(P<0.05),and reduce p62 protein expression(P<0.05).Conclusion Modified Guizhi Fuling Pills may exert therapeutic effects on DKD by regulating the AMPK-FOXO1-autophagy axis.

Objective To systematically search,evaluate,and summarize the evidence for risk management of breast and ovarian cancers in carriers of breast cancer susceptibility gene 1/2(BRCA1/2)mutations.Methods A systematic search was conducted in BMJ Best Practice,UpTo-Date,the National Guideline Clearinghouse(NGC),the National Institute for Health and Care Ex-cellence(NICE),the Scottish Intercollegiate Guidelines Network(SIGN),the Guidelines Interna-tional Network(GIN),the New Zealand Guidelines Group(NZGG),the Canadian Medical Associa-tion Infobase(CMA InfoBase),the Registered Nurses' Association of Ontario(RNAO),the National Comprehensive Cancer Network(NCCN),Cancer Care Ontario(CCO),the Medlive website,the American Society of Clinical Oncology(ASCO),the European Society for Medical Oncology(ESMO),the American Cancer Society(ACS),the American College of Obstetricians and Gynecologists(ACOG),the Joanna Briggs Institute(JBI),the Cochrane Library,PubMed,Web of Science,Em-base,CINAHL,ProQuest,ClinicalTrials.gov,China National Knowledge Infrastructure,Wanfang Data,VIP Database,and SinoMed for evidence related to risk management of breast and ovarian canc-ers in BRCA1/2 mutation carriers,including clinical decisions,guidelines,systematic reviews,expert consensus,and evidence summaries.The search period was from the inception of each database to September 20,2024.Results A total of 14 articles were included,comprising 1 clinical decision,8 guidelines,and 5 expert consensus documents.Based on five themes-risk assessment,risk moni-toring,risk-reducing surgery,pharmacologic prevention,and health guidance,a total of 24 pieces of evidence were summarized.Conclusion The evidence summarization process in this study is standardized,and the summarized evidence is relatively comprehensive.Healthcare professionals should comprehensively consider patients' individual characteristics,family history,personal prefer-ences,and the accessibility of healthcare resources to achieve effective prevention and control of he-reditary tumor risks.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.

The periodontal ligament (PDL) plays a crucial role in transmitting and dispersing occlusal force, acting as mechanoreceptor for muscle activity during chewing, as well as mediating orthodontic tooth movement. It transforms mechanical stimuli into biological signals, influencing alveolar bone remodeling. Recent research has delved deeper into the biological and mechanical aspects of PDL, emphasizing the importance of understanding its structure and mechanical properties comprehensively. This review focuses on the latest findings concerning both macro- and micro- structural aspects of the PDL, highlighting its mechanical characteristics and factors that influence them. Moreover, it explores the mechanotransduction mechanisms of PDL cells under mechanical forces. Structure-mechanics-mechanotransduction interplay in PDL has been integrated ultimately. By providing an up-to-date overview of our understanding on PDL at various scales, this study lays the foundation for further exploration into PDL-related biomechanics and mechanobiology.
Periodontal Ligament/cytology* ; Humans ; Biomechanical Phenomena ; Mechanotransduction, Cellular/physiology* ; Stress, Mechanical

Objective To investigate the effect of dexmedetomidine(Dex)on bone loss in tail-suspended rats and primarily explore its regulatory mechanism on bone metabolism.Methods A total of 30 male rats were randomly divided into a control group,a model group,and a Dex group,with 10 animals in each group.Rat model of osteoporosis was established by hind limb suspension for 4 weeks.Dex at a dose of 10 μg/kg was given intraperitoneally,once every other day from the day of tail suspension.And equal amount of normal saline was given to the control and model group.Bone histological staining was used to observe the trabecular bone area fraction.Biomechanical three-point bending test was employed to measure the maximum load,stiffness,and fracture energy.Dual calcein/alizarin red fluorescence labeling and tartrate resistant acid phosphatase(TRAP)staining were applied respectively to detect the mineral apposition rate and bone formation rate as well as the number of osteoclasts on bone surfaces.Secondly,after primary osteoblasts were isolated from the tibiae of tail-suspended rats and then treated with 1 nmol/L Dex,the proportion of alkaline phosphatase(ALP)-positive osteoblasts and the activity of the enzyme were detected by ALP staining and activity test.qRT-PCR was applied to measure the expression of osteogenic activity-related factors,including osteocalcin(Ocn),Runt related transcription factor 2(Runx2),Osterix protein(Osx),and type 1 collagen(Col1).Results The animal experiments revealed that Dex treatment significantly increased the tibial trabecular bone area fraction,inhibited the decrease in bone mechanical strength,and enhanced the mineralization deposition rate and new bone formation rate of trabecular bone in the tail-suspended rats(all P＜0.001).The in vitro experiments showed that Dex treatment obviously improved ALP activity and the number of ALP-positive osteoblasts in primary osteoblasts isolated from tail-suspended rats(P＜0.01),and up-regulated the expression levels of osteogenic differentiation-related genes,such as Ocn,Runx2,Osx and Col1(P＜0.01).Conclusion Dex exerts anti-bone loss effect in tail-suspended rats,which may be associated with its stimulation on osteoblast-mediated bone formation.