Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Objective:This study aims to investigate the influence of microvessel density（MVD） and microlymphatic vessel density（MLVD） on the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to develop a nomogram prediction model for prognosis based on pathological characteristics. Methods:A retrospective analysis was conducted on clinicopathological and follow-up data from HPSCC patients who underwent surgical treatment at our institution between June 2010 and June 2020. Immunohistochemical staining was performed on tumor tissues and adjacent normal margin tissues to evaluate MVD and MLVD. The associations among MVD, MLVD, and clinicopathological features were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors affecting overall survival（OS）. Based on these findings, a nomogram model was constructed and its predictive accuracy was assessed using C-index, receiver operating characteristic（ROC） curve, and calibration curve. Results:Both MVD and MLVD were significantly higher in HPSCC tumor tissues compared to normal tissues. Patients in the high MVD and high MLVD groups exhibited significantly lower OS rates than those in the low MVD and low MLVD groups. Multivariate Cox regression analysis revealed that N stage, recurrence, nerve invasion, lymph node capsule invasion, MVD, and MLVD were independent prognostic factors of OS. Based on these factors, a nomogram prognosis model was successfully constructed. The nomograms demonstrated superior performance in terms of C-index, area under the ROC curve, and calibration, outperforming the AJCC TNM staging system. Conclusion:Elevated MVD and MLVD levels are associated with poorer prognosis in HPSCC patients. The nomogram model based on pathological features provides valuable insights for clinical assessment and decision-making.
Humans ; Hypopharyngeal Neoplasms/blood supply* ; Prognosis ; Retrospective Studies ; Microvascular Density ; Nomograms ; Lymphatic Vessels/pathology* ; Male ; Female ; Middle Aged ; Carcinoma, Squamous Cell/blood supply* ; Microvessels/pathology* ; Lymphatic Metastasis ; Survival Rate

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

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*

In recent years, China has systematically enhanced its policy framework for innovative pharmaceuticals and medical devices and established a comprehensive, full-cycle support mechanism encompassing research and development, regulatory approval, manufacturing, reimbursement, and clinical application. This integrated approach has markedly accelerated the review-approval process and market entry of innovative medical products. Key regions including Beijing, Shanghai and the Guangdong-Hong Kong-Macao Greater Bay Area have demonstrated significant achievements through initiatives such as optimized clinical trial protocols, expedited regulatory pathways, and diversified payment models. Nevertheless, challenges persist, including restrictive performance metrics in hospital, underdeveloped multi-payer reimbursement systems, and interdepartmental coordination gaps. Moving forward, sustained efforts in policy harmonization, reimbursement mechanism innovation, core technology breakthroughs, and global collaboration should be critical to advancing the high-quality development of Chinese innovative pharmaceuticals and devices.

The accumulation of fatigue during military operations may lead to decreased operational efficiency and non-combat attrition,which can impact combat effectiveness.On-site monitoring and evaluation of fatigue during military operations,as an important means to keep track of military operations and bring about quick changes in training,underlie the combat effectiveness of military personnel.Focusing on the on-site monitoring and evaluation methods of fatigue during military operations,this paper reviews the determinants of such fatigue as well as on-site monitoring and comprehensive evaluation methods so as to provide reference for accurate and efficient evaluation of fatigue during military operations and for early warning of such fatigue.

Objective To investigate the application value of transumbilical single-port total laparoscopic hysterectomy by conventional instrument without uterine-lifting in the treatment of cervical lesions.Methods We selected 60 cases of total laparoscopic hysterectomy due to cervical high-grade squamous intraepithelial lesion(HSIL)or cervical cancer stage ⅠA1 from December 2021 to June 2023.According to the patients'preference,30 cases of single-port laparoscopy through the umbilicus and 30 cases of multi-port laparoscopy were performed,both using conventional instruments without uterine-lifting.The surgical indicators of the two groups were compared.Results No conversion to open surgery occurred in both groups,and no intraoperative injuries to the urinary system,bowel,or major blood vessels occurred.As compared with the multi-port group,the single-port group had significantly reduced amount of bleeding during surgery[(54.6±20.5)ml vs.(67.5±27.0)ml,P = 0.041],earlier anal exhaust time[(27.6±8.0)h vs.(32.2±9.0)h,P =0.040],and shorter total hospitalization time[(4.4±1.5)d vs.(5.1±1.2)d,P = 0.044].There were no significant differences in uterine weight,surgical time,and postoperative complications between the two group(P>0.05).The healing of the abdominal wall puncture wounds in both groups of patients were satisfied.There were no short-term complications related to the puncture device(such as puncture wound infection and bleeding)or long-term complications(such as umbilical hernia and incisional hernia).Conclusion Transumbilical single-port total laparoscopic hysterectomy without uterine-lifting presents advantages of less intraoperative bleeding,faster postoperative recovery,and almost no scarring,with complications similar to traditional laparoscopic surgery.

Objective:Distribution and antibiotic resistance of pathogen isolated from children with intra-abdominal infection (IAI) associated sepsis in the intensive care unit (ICU) were analyzed to provide a reference for the empirical anti-infective treatment of IAI in children.Methods:We retrospectively analyzed the data of 116 children with culture-positive IAI-associated sepsis admitted to Children's Hospital of Zhejiang University School of Medicine from January 2019 to December 2021. Clinical isolation and drug resistance analysis were conducted based on different years of onset, locations of onset, and primary diseases.Results:A total of 186 strains of pathogens causing children with IAI-associated sepsis in ICU were collected. The distribution and antibiotic resistance of pathogen were as follows: the percentages of gram-positive bacteria, gram-negative bacteria, and fungi were 53.2%, 40.9%, and 5.9%, respectively; the top four strains were Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, accounting for 57.0% of all isolates; Enterococcus faecium(19.9%) and Enterococcus faecalis (10.2%) were the dominating gram-positive bacteria; Escherichia coli (13.4%) and Klebsiella pneumoniae (13.4%) were more common gram-negative bacteria; Fungi were dominated by Candida albicans (3.8%).Fifty-seven strains of gram-positive bacteria were detected in 61 children with infectious diseases, mainly Enterococcus faecium (28 strains). There were 53 gram-negative strains, mainly Klebsiella pneumoniae (21 strains). Thirty-two strains of gram-positive bacteria were detected in 40 children with digestive tract malformation, and Enterococcus faecalis (six strains) were the most common. There were 14 gram-negative strains, mainly Escherichia coli (six strains). In 13 children with malignant tumors of digestive system, nine strains of gram-positive bacteria were cultured, and Enterococcus faecium (four strains) was the most common. There were eight gram-negative strains, mainly Escherichia coli (four strains).In the 46 community-acquired IAI patients,30 gram-positive isolates were cultured,mainly including Enterococcus faecium (12 strains), Staphylococcus epidermidis (seven strains), and Viridans streptococci (six strains); Forty gram-negative isolates mainly contained Escherichia coli (16 strains), Klebsiella pneumoniae (14 strains), and Enterobacter cloacae (five strains). In the 70 hospital-associated IAI patients, 69 gram-positive isolates such as Enterococcus faecium (25 strains), Enterococcus faecalis (17 strains), Enterococcus gallinarum (eight strains), and Staphylococcus aureus (seven strains) were cultured;Tirty-six gram-negative isolates were dominated by Klebsiella pneumoniae (11 strains), Escherichia coli (nine strains), Pseudomonas aeruginosa (four strains), and Acinetobacter baumannii (four strains). The mixed infection rate of clinical pathogens was up to 46.6%, and the overall resistance rate was 43.4%, in which gram-negative bacteria had high sensitivity to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, and tigecycline.The detection rates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum β-lactamases were 36.0% and 24.6%, respectively, with 100% sensitivity to tigecycline. Gram-positive bacteria showed 100% sensitivity to vancomycin, linezolid, and tigecycline. Conclusion:Pathogen isolated from children with IAI-associated sepsis in ICU were dominated by Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis,respectively. Before confirmation of pathogenic bacteria, antibacterial agents can be selected according to the infection type. It is important to note that a single broad-spectrum antibacterial agent or combination medication can be considered the initial empirical choice due to the large variety of pathogens, high rates of mixed infections, and high overall resistance.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Background Major depressive disorder and insomnia often coexist,and the two may share a mechanism of pathogenesis and be affected by common underlying genes with strong pleiotropic effects.Previous genome-wide association studies(GWAS)mainly focused on single-gene morphological characters analysis,which impose limitations on showing possible pleiotropic effects.Objective To identify genetic loci related to insomnia and major depressive disorder,and to examine whether there are common genetic factors underlying both insomnia and depression.Methods The GWAS data for major depressive disorder originates from the Psychiatric Genomics Consortium(PGC),which comprises a total of 246363 depressive cases and 561190 controls.The insomnia GWAS data was downloaded from Sleep Disorder Knowledge Portal,involving 1331010 participants.Then the conditional false discovery rate(cFDR)and conjunction cFDR(ccFDR)were utilized to identify the genetic loci associated with major depressive disorder and insomnia,and pathway enrichment analysis was performed to examine the biological functions of these loci.Results A significant pleiotropic effect was detected between major depressive disorder and insomnia.By leveraging pleiotropic enrichment,21 susceptibility loci(17 novel loci)for major depressive disorder and 38 susceptibility loci(28 novel loci)for insomnia were identified with the threshold of cFDR<0.01.A total of 16 pleiotropic loci(15 novel loci)related to both major depressive disorder and insomnia were identified with the threshold of ccFDR<0.05.pathway enrichment analysis indicated that the susceptibility loci were mainly enriched in synaptic transmission pathway,such as postsynaptic density(GO:0014069,P=4.91E-04,FDR=4.84E-03),asymmetric synapse(GO:0032279,P=5.09E-04,FDR=4.84E-03),and regulation of postsynaptic membrane neurotransmitter receptor levels(GO:0099072,P=5.11E-04,FDR=1.69E-02).Conclusion A significant pleiotropic enrichment is found between major depressive disorder and insomnia,and the comorbidity mechanism is related to synaptic transmission.