Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Medication reconciliation plays a key role in improving patient medication safety,reducing inappropriate polypharmacy,and promoting the high-quality development of pharmaceutical services.Compared to advanced international guidelines,China's medication reconciliation service standards have deficiencies in areas such as definition and process design,and multidisciplinary team building.There is a need to establish a comprehensive medication reconciliation effect evaluation index system,develop pharmacist-led multidisciplinary teams,promote the advancement of artificial intelligence and big data technologies,and strengthen outpatient and community medication reconciliation coverage,thereby contributing to the high-quality development of pharmaceutical services in China.

Postherpetic neuralgia is a common chronic and intractable neuropathic pain.In recent years,a growing number of neuroimaging studies have used MRI to explore the different effects of postherpetic neuralgia on brain structure and function.This paper reviews the research progress of postherpetic neuralgia from various MRI techniques,revealing the remodeling mechanism of the central nervous system,such as abnormalities in various brain functional networks and activation of pain-related brain regions,to provide a reference for clinical auxiliary diagnosis and objective evaluation.

Objective:Postoperative neurosurgical bacterial meningitis (PNBM) has been frequently reported, but fewer studies have focused on the contemporaneous comparison of clinical features of PNBM caused by different pathogenic bacteria. This study aimed to simultaneously investigate the clinical characteristics and outcomes of PNBM by Gram-positive bacterial(GPB) or Gram-negative bacterial (GNB) infection.Methods:Inpatients with PNBM at our institution were recruited between February 2013 and October 2023. These PNBM patients were categorized into two groups: GPB infection and GNB infection. Data from electronic medical records were collected and analyzed.Results:A total of 401 patients with PNBM were finally included, with 78 (19.5%) having GPB infections and 323 (80.5%)having GNB infection. The average age of the patients was 56 years, and 55.1% were male. Compared to the GPB group, PNBM patients with GNB infection had significantly higher SOFA and APACHE Ⅱ scores, higher proportions of hyperthermia (body temperature>39°C) and altered consciousness, increased ratios of postoperative cerebral hemorrhage or intracranial aneurysm, as well as greater needs for ICU treatment and mechanical ventilation (all P <0.05). The proportions of inflammatory indicators such as blood CRP and PCT≥2 ng/mL, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly higher in the GNB group (all P<0.05). In contrast, The concentrations of hemoglobin and albumin were substantially lower in this group(both P <0.05). Additionally, the cerebrospinal fluid in the GNB group showed significantly higher nucleated cell counts, protein concentration, and adenosine deaminase concentration, and but lower glucose level (all P <0.001). A total of 426 bacterial strains were isolated, with 343 strains (80.5%) being GNB and 83 strains (19.5%) being GPB. Among these, 25 (6.2%) patients had 2 or more gram-positive or gram-negative bacterial infections. The proportions of multidrug-resistant (MDR) bacteria and intrathecal treatment were higher in the GNB group (80.5% vs. 68.7%, 36.5% vs. 2.6%, respectively), while the ratio of correct empirical antibiotic treatment was significantly lower (30.3% vs. 80.0%) (all P <0.05). In terms of outcomes, the length of stay in the ICU was significantly longer in the GNB group [(median (interquartile range, IQR): 11.5 (5.25,22.75) vs. 17.0 (9.0,30.0), P <0.01)], and the rate of septic shock (9.3% vs. 2.6%), poor prognosis (GCS≤8 at discharge) (65.9% vs. 32.1%), and 28-day hospital mortality rate (34.4% vs. 10.3%) were significantly higher compared to the GPB group (all P <0.05). However, there were no differences in 7-day hospital mortality and total hospitalization time. Conclusions:Gram-negative bacterial infections are more prevalent than Gram-positive bacterial infections in PNBM, and they are also associated with more severe symptoms, abnormal cerebrospinal fluid findings, higher severity, and more treatment difficulty. Despite comparable short-term (7-day) mortality rates between Gram-positive and Gram-negative bacterial infections, Gram-negative bacterial infections result in higher medium- to long-term (14-day and 28-day) case-fatality rates among patients with post-neurosurgical bacterial meningitis and are associated with overall poorer prognosis, warranting greater attention from clinicians.

Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.