Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

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.

AIM: To investigate how angles kappa and alpha affect postoperative visual quality in patients with multifocal intraocular lens(mIOLs)implantation.METHODS: Retrospective cases series. A total of 46 patients(46 eyes)who underwent phacoemulsification were subsumed. The correlation between Preoperative angles kappa and alpha, wave-front aberrations and objective visual quality of cornea, internal, and total eye after surgery were analyzed using iTrace.RESULTS: The magnitude of angle kappa was negatively correlated with internal and total modulation transfer function(MTF)at 3 mm; the magnitude of angle kappa was positively correlated with astigmatism, trefoil, higher-order aberrations(HOAs)of both internal and total eye at 3 mm. The magnitude of angle alpha was negatively correlated with total MTF and total Strehl ratio at 3 mm. The magnitude of angle alpha was positively correlated with corneal coma at 5 mm, internal astigmatism at both 3 mm and 5 mm, and total spherical aberration(SA)at 3 mm. Multivariate linear regression analysis showed that, among candidate independent variables(kappa, alpha, astigmatism, SA, coma, trefoil, and HOAs), astigmatism is the only independent factor for altering corneal MTF at 3 mm and 5 mm; astigmatism and HOAs emerged as independent factors for altering internal MTF at 3 mm and 5 mm, and total MTF at 3 mm; astigmatism, SA and HOAs emerged as independent factors for altering total MTF at 5 mm.CONCLUSION: With greater preoperative angle kappa or angle alpha, patients who accept mIOL implantation tend to have larger internal astigmatism and HOAs, which resulting in poor visual quality, especially those with small pupil size.

Objective To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assis-tance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury.Methods A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022.Among them,39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of(44.98±7.33)years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy in-cluding 24 males and 13 females with an average age of(44.37±10.82)years old.Among them,42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation(INFIX)or suprapubic support screws to fix the anterior pelvic ring.Postoperative follow-up time,operation time,complications of the two groups were compared.Results of Matta reduction criteria,Majed efficacy evaluation,the CT grading and the rate of secondary surgical revision were com-pared.Results The nailing time of(32.63±7.33)min in CT group was shorter than that of(52.95±10.64)min in C-arm group(t=-9.739,P＜0.05).The follow-up time between CT group(11.97±1.86)months and C-arm group(12.03±1.71)months were not statistically significant(P＞0.05).The postoperative complication rates between two groups were not statistically significant(x2=0.159,P＞0.05).Results of Matta reduction criteria(Z=2.79,P＜0.05),Majeed efficacy evaluation(Z=2.79,P＜0.05),CT grading(Z=2.83,P＜0.05)in CT group were better than those in C-arm group(P＜0.05);the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group(x2=5.641,P＜0.05).Conclusion Compared with traditional C-arm fluoroscopy,intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time,high accuracy and safety,and significant decrease in postoperative sec-ondary revision rate,and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Objective:To investigate the risk factors and predictive value on acute kidney injury (AKI) following surgery, and to elucidate the relationship between platelet/white blood cell ratio (PWR) and AKI.Methods:A retrospective case-control study was conducted. The patients who underwent surgery admitted to Honghui Hospital of Xi'an Jiaotong University from January 2019 to January 2023 were enrolled. The patients who developed AKI during the postoperative hospital stay were categorized as the AKI group, while those with normal renal function or not meeting AKI criteria were categorized as the non-AKI group. Demographic information, clinical characteristics, perioperative medication usage, surgical related information, and preoperative and postoperative laboratory indicators were collected. Binary multivariate Logistic regression analysis was used to identify risk factors for postoperative AKI. Receiver operator characteristic curve (ROC curve) was plotted to assess the predictive efficacy of postoperative PWR for postoperative AKI.Results:A total of 420 patients were enrolled finally, with 72 developing AKI during hospitalization and 348 not developing AKI. Compared with the non-AKI group, the patients in the AKI group had a higher proportion of hypertension and coronary heart disease, a more usage of angiotensin converting enzyme inhibitor (ACEI), mannitol and vancomycin but a less usage of hydroxyethyl starch, a longer duration from injury to surgery and postoperative hospital stay, a greater intraoperative blood transfusion volume, a lower preoperative albumin (Alb), blood sodium, blood chlorine but a higher serum creatinine (SCr), blood urea nitrogen (BUN)/Alb ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP), and a higher postoperative white blood cell count (WBC), BUN, SCr, BUN/Alb ratio, blood potassium, and blood phosphorus but a lower platelet count (PLT), PWR, and Alb. Binary multivariate Logistic regression analysis revealed that perioperative usage of hydroxyethyl starch [odds ratio ( OR) = 8.595, 95% confidence interval (95% CI) was 4.112-17.964, P < 0.001], prolonged duration from injury to surgery ( OR = 1.084, 95% CI was 1.034-1.137, P = 0.001), increased intraoperative blood transfusion volume ( OR = 1.001, 95% CI was 1.000-1.002, P = 0.017) were risk factors for AKI following surgery, and increased postoperative PWR was protective factor ( OR = 0.930, 95% CI was 0.894-0.967, P < 0.001). ROC curve analysis indicated that the area under the ROC curve (AUC) of postoperative PWR for predicting postoperative AKI was 0.684 (95% CI was 0.615-0.754); at the optimal cut-off value of 19.34, the sensitivity was 63.8%, and the specificity was 69.8%. Conclusions:Postoperative PWR is an independent risk factor for AKI in patients undergoing surgery. Postoperative PWR reduction in surgical patients can assist in predicting the occurrence of postoperative AKI.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Objective:To analyze the factors for low libido in male patients with sexual dysfunction and provide some evidence for the clinical diagnosis and treatment of the condition.Methods:We retrospectively analyzed the clinical data on 111 cases of sex-ual dysfunction(including disorders in erection,ejaculation or libido)treated in the Zhengzhou University First Hospital from June to September 2023.According to the patients'complaints of low libido or accompanied symptoms,we divided them into a normal libido group(n=68)and a low libido(n=43),obtained their scores on IIEF-5,Premature Ejaculation Diagnostic Tool(PEDT),13-1-tem Self-Rating Libido Scale for Males(SRLS-M),Patients'Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7),examined the levels of the sexual hormones FSH,LH,PRL,T,free testosterone(fT),E2,?insulin-like growth factor 1(IGF-1)and growth hormone(GH),compared the basic parameters between the two groups,and analyzed their correlation with the libido values.Results:The IIEF-5,PEDT and libido scores and IGF-1 level were significantly higher and the GAD-7 score remark-ably lower in the normal than in the low libido group(P＜0.05),but no statistically significant differences were observed between the two groups in the PHQ-9 score and the levels FSH,LH,PRL,T,fT,E2,T/E2 and GH(P＞0.05).The libido value was correla-ted positively with the I1EF-5(r=0.28,P＜0.01)and PEDT scores(r=0.29,P＜0.01)and IGF-1 level(r=0.23,P＜0.05),but negatively with the GAD-7 score(r=-0.21,P＜0.05).Conclusion:Low libido results from multiple factors,which cannot be fully explained by sexual hormone levels but is closely related to the decreased level of IGF-1 and severity of ED and anxiety.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.