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.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

BACKGROUND:For elderly patients with traumatic hip fractures,the related factors of prognosis are very complex,and the integrity of the lateral wall is one of the influencing factors.It is of important clinical value to understand the effect of lateral wall injury on the prognosis of femoral intertrochanteric fracture. OBJECTIVE:To evaluate the relationship between the integrity of the lateral wall and hip functional recovery and other outcomes in patients with femoral intertrochanteric fractures. METHODS:Totally 82 patients with femoral intertrochanteric fractures were screened and all patients received proximal femoral nail antirotation fixation.According to the thickness of the lateral wall,the patients were divided into the lateral wall intact group(n=31)and lateral wall risk group(n=51).The perioperative indexes,weight-bearing time,fracture healing time,hip joint function and range of motion,postoperative pain and complications were compared between the two groups. RESULTS AND CONCLUSION:(1)The time of hospitalization and the number of fluoroscopies during operation in the lateral wall intact group were significantly lower than those in the lateral wall risk group(P<0.05),but there was no significant difference in other perioperative indexes.(2)Both groups were able to get down to the ground early after surgery and finally complete weight-bearing,but in the lateral wall risk group,the time of fracture healing was longer;the time of complete weight-bearing was significantly delayed;the Harris score of the last follow-up was lower;the range of motion of hip extension and flexion and neck trunk angle on the affected side were smaller(P<0.05).(3)There was no significant difference in the incidence of postoperative complications between the two groups,but the overall incidence of complications in the lateral wall intact group was significantly lower(P<0.05).(4)In summary,after internal fixation of proximal femoral nail antirotation,patients with the intact lateral wall had a relatively better prognosis than those with risk lateral wall.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

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.

Objective:To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion.Methods:A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t-test, Mann-Whitney U test, Wilcoxon signed rank test, χ2 test or corrected χ2 test as appropriate. Results:Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes; t=-2.392, P=0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t=10.604, P<0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days; t=2.480, P=0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups ( χ2=0.278, P=0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups ( t=1.607, P=0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups ( t=-1.003, P=0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was ( M(IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences ( Z=-3.937, P<0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ2=1.765， P=0.184). Conclusion:3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

Objective:To analyze the external quality control assessment results of fluoride testing laboratories in endemic disease prevention and control institutions nationwide from 2006 to 2023, investigate the quality control capabilities of these laboratories in various provinces, prefectures, cities, and counties nationwide, and ensure the accuracy and reliability of surveillance data on endemic fluorosis nationwide.Methods:Using retrospective analysis, the external quality control assessment results of all participating fluoride testing laboratories of national endemic disease prevention and control institutions from 2006 to 2023 were summarized and analyzed. The assessment results from 2006 to 2008 were tested for outliers using Grubbs method, homogeneity of variance using Cochran method, excluding the assessment data of unqualified laboratories, calculating the total mean and total standard deviation, Z-score method was used to test the assessment of laboratories, and statistical analysis and judgment were done when the result of │Z│ < 3. The assessment results from 2009 - 2023 were obtained from all laboratories. In 2010, two tests were conducted in the first and second half of the year, and the Z-ratio scores of each laboratory were calculated using robust statistics. When │Z│≤2, the assessment was qualified; when 2 < │Z│ < 3, the assessment was basically qualified; when│Z│≥3, the assessment was unqualified, and the consensus value came from all participating laboratories in the assessment.Results:From the beginning of quality control operation in 2006 to 2023, the number of laboratories participated in external quality control assessments had significantly increased. The number of laboratories participated in water fluoride assessment increased from 30 in 2006 to 1 277 in 2023, and the number of laboratories participated in urine fluoride assessment increased from 29 to 497. The number of laboratories participated in the brick tea fluorine assessment had increased from 43 in 2014 to 193 in 2023. The assessment results showed that when │Z│ < 3, the total qualified rate of fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 95.2%, with the lowest being 87.1% (27/31) in 2008 and the highest being 100.0% (394/394) in 2014. When │Z│≤2, the total feedback pass rate was 88.4%, with the lowest being 79.3% (288/363) in the first half of 2010 and the highest being 99.5% (392/394) in 2014. The assessment results showed that when │Z│ < 3, the total pass rate of urine fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 98.0%, with the lowest being 86.2% (25/29) in 2006 and 2007, respectively, and the highest being 100.0% (68/68) in 2014. When │Z│≤2, the total qualification rate was 93.7%, with the lowest being 86.5% (64/74) in the second half of 2010 and the highest being 100.0% (68/68) in 2014. The assessment results showed that when│Z│ < 3, the total pass rate of extra-fluoride quality control of brick tea in fluoride testing laboratories of national endemic disease control institutions was 95.4%, with the lowest being 85.0% (164/193) in 2023, and the highest being 100.0% (43/43, 51/51, 79/79) in 2014, 2015 and 2016, respectively. When │Z│≤2, the total pass rate was 89.2%, with the lowest being 72.7% (32/44) in 2017 and the highest being 100.0% (43/43) in 2014. From 2009 to 2023, there were a total of 21 provincial-level laboratories that passed the water fluoride detection assessment, including 3 provinces where all prefecture level and county-level laboratories were qualified. The assessment results of urinary fluorine showed that there were 11 qualified provincial-level laboratories and 1 prefecture-level laboratory. From 2014 to 2023, the assessment results of brick-tea fluorine showed that there were 5 provincial-level laboratories that passed the tea fluorine testing assessment and no prefecture-level laboratory.Conclusions:Conclusion: From 2006 to 2023, the number of fluoride testing laboratories participating in external quality control assessment has increased year by year, and most provincial, municipal and county-level laboratories have good fluoride testing capabilities, which can meet the testing needs of endemic disease prevention and monitoring. For some laboratories with problems, targeted rectification should be carried out to improve the quality of detection, in order to provide better technical support for the monitoring of endemic fluorosis areas.

Objective To measure and comprehensively analyze the operation efficiency of coronary heart disease Center of National Regional Medical Center for Cardiovascular Disease from the dimensions of department service in-come,department service quality,department service efficiency and department service benefit,and put forward targeted operation management optimization strategies based on the analysis results.Methods The operation effective-ness evaluation index of CHD centers in sample hospitals from 2020 to 2022 was measured by the empirical re-search method from the overall level of the center and the level of clinical departments,and the scores were com-pared and analyzed.Results From 2020 to 2022,the operation effectiveness evaluation index of CHD centers in sam-ple hospitals showed a good trend,increasing from 80.57 points to 82.86 points.The 3-year average score was 81.74;Among them,the score rate of department service benefit dimension is higher,the average is 96.64％;The score rate of department service efficiency was lower,with an average of 68.53％.The departments with the lowest operational efficiency scores from 2020 to 2022 are all A2 departments,with 74.39,72.41 and 75.89 scores respec-tively,mainly due to the relatively low scores of A2 departments in the dimensions of department service revenue and department service efficiency.Conclusion The results of clinical department operation effectiveness evaluation can provide the evidence-based basis for hospital operation management,and hospitals can establish benchmarking management departments according to the evaluation results and take targeted measures to improve the comprehen-sive operation efficiency of departments.