ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

Objective:To develop a continuous non-invasive blood pressure measurement device(NC-BPM)and verify the accuracy of that in monitoring blood pressure.Methods:A NC-BPM type of non-invasively continuous blood pressure measurement device(NC-BPM for short)was developed.The entire system consisted of four modules included one sensor which shape was finger cot,one unit of signal acquisition and pressure control,one calibration system for height and one host.The Omron J760 electronic sphygmomanometer(J760)and the CNAP Monitor500 continuous non-invasive blood pressure monitoring system(CNAP Monitor500)were used as the reference sphygmomanometer of verifying accuracy of the monitored blood pressure.The blood pressures of 25 subjects at three stages included static stage,blood pressure change stage and stage post calibration were respectively measured according to the standard test procedure of wearable sleeveless blood pressure measurement device of Institute of Electrical and Electronics Engineers(IEEE).Results:Both NC-BPM and CNAP Monitor500 collected 13753 data points,and there were high correlation in systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean blood pressure(MAP)between the two devices(r=0.96,0.97,0.98,P<0.05).A total of 379 data points were collected by Omron J760,and there were high correlation in SBP and DBP between NC-BPM and Omron J760(r=0.98,0.95,P<0.05).According to the standards of British Hypertension Society(BHS)and the American Association for the Advancement of Medical Instrumentation(AAMI)to conduct grade evaluation,and the proportions of the SBP differences between NC-BPM and CNAP Monitor500 within the ranges of 0～5 mmHg,0～10 mmHg and 0～15 mmHg were respectively 85.01%,97.60%and 99.47%,and the proportions of the DBP differences between them within the three ranges were respectively 84.34%,99.85%and 100%,and the proportions of the MAP differences were respectively 92.66%,99.72%and 99.96%,all of which belonged to BHS grade A.The pressure difference values of measured SBP,DBP and MAP between the two devices were respectively(0.67±5.07)mmHg,(2.43±2.87)mmHg and(1.43±2.89)mmHg,which were within the(5±8)mmHg of AAMI standard range.The proportions of the SBP differences between NC-BPM and Omron J76 within the ranges of 0～5 mmHg,0～10 mmHg and 0～15 mmHg were respectively 79.95%,97.36%and 100%,and the proportions of the DBP differences between them within the three ranges were respectively 89.71%,99.74%and 100%,all of which belonged to BHS grade A.The difference values of systolic and diastolic blood pressures of brachial artery between the two devices were respectively(1.57±4.18)mmHg and(0.57±5.20)mmHg,which were within the(5±8)mmHg of AAMI standard range.Conclusion:The NC-BPM device has passed the first stage of clinical trials in accordance with IEEE standards,which can proceed to the next stage of clinical verification trials.

Objective:To elucidate the etiological and epidemiological characteristics and epidemiological patterns of viral acute respiratory infections (ARI) in Shanghai during 2023, with the aim of providing robust laboratory evidence for effective prevention and control strategies against related respiratory diseases and facilitating risk assessment.Methods:Respiratory pathogens were detected in the clinical surveillance specimens submitted by sentinel hospitals through multiplex PCR, as part of the multi-pathogen surveillance of acute respiratory infections in Shanghai during 2023. The obtained detection result were statistically analyzed in conjunction with sample information.Results:The positive detection rate of viral pathogens in 2023 was 21.17% (984/4 648), with rates of 33.53% (504/1 503) observed in ILI cases and 15.62% (480/3 145) in SARI cases. Influenza A virus (FluA) was the predominant virus detected, accounting for 13.7% (637/4 648). Other viruses identified in the surveillance samples included influenza B virus (Flu B), human rhinovirus/enterovirus (HRV/HEV), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (HBoV). Regarding temporal distribution, HRV/HEV and RSV exhibited the highest detection rates during the second quarter at 2.27% each (28/1 236). PIV had its peak during the third quarter at a rate of 2.49% (35/1 405), and HMPV showed prevalence mainly during the third and fourth quarters, with detection rates of 2.63% (37/1 405) and 2.35% (32/1 360), respectively.Conclusions:In acute respiratory infection surveillance cases in Shanghai in 2023, Flu A emerged as the predominant respiratory pathogen. The detection rate of HMPV ranked second only to Flu A, while other respiratory viruses such as HRV/HEV, RSV, and PIV were detected during different seasons and co-circulated. The prevalence of various respiratory viruses varied among different infected populations and over times.

Objective To plan microwave antenna puncture direction effectively and realize personalized preoperative simulation by exploring microwave ablation(MWV)outcomes of lung cancer based on real anatomical model.Methods Firstly,a personalized MWA simulation model consisting of the lung tissue,tumor and vascular system was constructed based on the lung CT data of real patients.Secondly,the MWA effect was simulated by coupling 2 physical fields including an electromagnetic field and a biological heat transfer field,so as to determine the volume of the ablation thermocoagulation zone and the temperature distribution of the lung tissue.Finally,the effects of the vascularized network on the ablation results were quantitatively evaluated in terms of conductivity and blood perfusion,and the ablation results were analyzed with different distances between the large vessels and the antennae(5 and 10 mm from the antennae tips)and puncture angles(large vessels parallelling or intersecting with the antennae tips).Results The vascularized network reduced the volume of the thermocoagulation zone by 0.5％to 3.7％,and blood perfusion made the ablation temperature and the volume of the thermocoagulation zone decreased significantly.The cooling effect gradually diminished with the increase of the distance between the large vessels and the antenna.With the same treatment parameters,the thermocoagulation zone formed when the large vessels paralleled with the antenna was obviously larger than that when the vessles intersected with the antenna.Conclusion Personalized MWA simulation analysis based on real CT data contributes to clarifying the temperature distribution and damage estimation close to the actual situation,which provides guidance and reference for precise treatment of the lung tumor and determination of microwave antenna puncture direction.[Chinese Medical Equipment Journal,2024,45(9):27-34]