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.

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population aging. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.
Humans ; Male ; Female ; Incidence ; Fractures, Bone/epidemiology* ; Middle Aged ; Adult ; Global Health ; Aged ; Global Burden of Disease ; Adolescent ; Child ; Young Adult ; Foot Injuries/epidemiology* ; Cost of Illness ; Child, Preschool ; Aged, 80 and over ; Infant

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

AIM To study the extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves(sbsl GUS).METHODS With granularity,water consumption,extraction time and extraction frequency as influencing factors,enzymatic activity as an evaluation index,the extraction process was optimized by orthogonal test on the basis of single factor test.The relationship between substrate(baicalin)concentration and enzymolysis rate,after which Vmax and Km were calculated,the effects of pH value,temperature and metal ion on enzymatic activity were investigated,pH stability and heat stability were evaluated.sbsl GUS was adotped in the enzymolysis of baicalin to prepare baicalein,then the effects of pH value,temperature,reaction time,initial substrate concentration and enzyme addition on transfer rate were investigated.RESULTS The optimal extraction process was determined to be 40 mesh for granularity,10 times for water consumption,15 min for extraction time,and 3 times for extraction frequency.The enzymolysis accorded with the kinetics of enzymatic reaction,Km was 0.006 3 mol/L,Vmax was 70.42 μmol/h,the strongest enzymatic activity was found at the pH value of 6.0,temperature of 45℃and metal ion of 100 mmol/L Cu2+,sbsl GUS demonstrated good stability at the ranges of 4.0-7.0 for pH value and 4-30℃for temperature.The optimal preparation process was determined to be 6.0 for pH value,45℃for temperature,more than 12 h for reaction time,67.2 mmol/L for initial substrate concentration,and 1 mL/0.269 mmol baicalin for enzyme addition,the transfer rate was 97.83%.CONCLUSION sbsl GUS enzymolysis exhibits high efficiency and mild condition,which can provide a simple preparation method for obtaining baicalein,and expand the application path of Scutellaria baicalensis stems and leaves.

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.