Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective:To evaluate the efficacy of rhomboid inter-costal and sub-serratus (RISS) block with ropivacaine-dexmedetomidine-dexamethasone for analgesia after thoracoscopic lobectomy.Methods:This study was a prospective, randomized, double-blind, controlled trial. From January 2021 to November 2023, 46 American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, undergoing elective video-assisted thoracoscopic lobectomy at the Second Affiliated Hospital of Nanjing Medical University, were selected and assigned into 2 groups ( n=23 each) using simple randomization: ropivacaine group (R group) and ropivacaine-dexmedetomidine-dexamethasone group (RDA group). RISS block was performed preoperatively, with 20 ml of the drug solution injected at the target points of the rhomboid-intercostal muscle and the serratus anterior-intercostal muscle. R group received 0.375% ropivacaine 40 ml, while RDA group received 40 ml of the mixture containing 0.375% ropivacaine, dexmedetomidine 1 μg/kg, and dexamethasone 8 mg. Postoperative analgesia was performed with oxycodone (When the patient′s numerical rating scale [NRS] score >4 in post-anesthesion care unit, oxycodone 2 mg was intravenously administered as needed until the NRS score <4, and then a patient-controlled analgesia pump was initiated). The time of the first postoperative analgesic requirement, NRS scores at rest and during coughing at 1, 3, 6, 12, 24 and 48 h postoperatively, cumulative consumption of oxycodone in the periods of 0-12 h, >12-24 h, and >24-48 h, time to first ambulation, and incidence of related adverse reactions within 48 h postoperatively were recorded. Results:Compared with R group, the time to the first analgesic requirement was significantly prolonged, the cumulative consumption of oxycodone in the first 0-12 h postoperatively was reduced ( P<0.001), and no statistically significant changes were found in the time to first ambulation, NRS scores at rest and during coughing, or the incidence of postoperative adverse reactions in RDA group ( P>0.05). Conclusions:RISS block using a combination of ropivacaine, dexmedetomidine and dexamethasone can significantly prolong block duration, reduce postoperative opioid analgesic consumption, and provide good safety for the patients undergoing thoracoscopic lobectomy.

Objective:To determine the median effective dose (ED 50) of oliceridine inhibiting the responses to the laryngeal mask airway insertion when combined with ciprofol in elderly patients. Methods:In this sequential trial, American Society of Anesthesiologists Physical Status classificationⅠ-Ⅲ elderly patients of either sex, aged ≥65 yr, with a body mass index of 18-30 kg/m 2, undergoing elective urological surgery under general anesthesia with laryngeal mask airway, were included in this study. Ciprofol 0.4 mg/kg was intravenously injected, the dose of oliceridine was determined by using modified Dixon′s up-and-down method (increment or decrement of 0.005 mg/kg), and the initial dose of oliceridine was 0.01 mg/kg. A positive response was defined as an increase in maximum mean arterial pressure or heart rate ≥20% within 3 min after inserting the laryngeal mask airway or occurrence of any one of these signs such as movement, coughing, frowning, mouth corner twitching, tearing, laryngospasm, or bispectral index value failing to drop below 60. The trial was terminated upon observing 7 positive-to-negative transition points, starting from the first occurrence of an alternation between positive and negative responses to laryngeal mask airway insertion. The ED 50 and 95% confidence interval of oliceridine inhibiting the responses to the laryngeal mask airway insertion was calculated when combined with ciprofol in elderly patients. Results:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion was 0.027 mg/kg, and the 95% confidence interval was 0.008-0.048 mg/kg when combined with ciprofol 0.4 mg/kg. Conclusions:The ED 50 of oliceridine inhibiting the response to laryngeal mask airway insertion is 0.027 mg/kg when combined with ciprofol 0.4 mg/kg in elderly patients.

Objective:To explore the optimization potential of clinical target volume (CTV) delineation proposed in the guidelines of the Oncology Group (RTOG), the Francophone Group of Urological Radiotherapy (GFRU), and the European Society for Radiotherapy and Oncology (ESTRO) based on prostate bed local occurrence patterns after radical prostatectomy identified using prostate-specific membrane antigen positron emission tomography (PSMA PET).Methods:A retrospective analysis was conducted on patients with local prostate bed recurrence after radical prostatectomy who underwent PSMA PET at the Department of Nuclear Medicine, Peking University First Hospital from September 2021 to February 2024. The central point of each recurrence was marked. A six-zone method was established based on prostate bed anatomy and the characteristics of cross-sectional imaging. Then, the positional relationships (within or outside) were recorded with respect to recurrences and CTV defined by the RTOG, GFRU, and ESTRO (CTV RTOG, CTV GFRU, and CTV ESTRO), followed the analysis of the recurrence rates and distribution characteristics of various zones. Results:A total of 63 patients with prostate bed recurrence after radical prostatectomy were enrolled in this study, including 97 recurrences. The recurrence rates in the six zones were as follows: 10% of zone 1, 22% of zone 2, 29% of zone 3, 2% of zone 4, 12% of zone 5a, 18% of zone 5b, and 7% of zone 6. Among these zones, zones 2 and 3 showed the highest and second-highest recurrence rates, respectively. CTV GFRU and CTV ESTRO completely covered zones 2 and 3, while CTV RTOG covered zone 2 completely and zone 3 partially. Zone 4, characterized by a low recurrence rate, was not covered by CTV GFRU and CTV ESTRO but was entirely covered by CTV RTOG. Zone 5a, with a recurrence rate of 12%, was completely covered by CTV RTOG but was partially covered by CTV GFRU and CTV ESTRO. The range of 1.3 cm in front of the posterior wall of the bladder covered all recurrences in zone 5a. Conclusions:For CTV delineation of the prostate cancer surgical bed, zone 4, the anterior half of the bladder above the pubic symphysis midpoint, should be contracted due to the low recurrence rate in this zone. In contrast, the anterior boundary above the pubic symphysis midpoint should extend to 1.3 cm in front of the posterior wall of the bladder to completely cover the recurrence zones.

Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Objective To investigate the correlation between the expression level of absent in melanoma 2(AIM2)in serum and the severity of acute cerebral infarction(ACI),and to evaluate the value of AIM2 in predicting early neurological deterioration(END)after intravenous thrombolysis with alteplase in ACI patients.Methods A total of 150 ACI patients were enrolled in ACI group,and an-other 30 healthy individuals physical examination were selected as control group.ACI patients were further divided into mild,moderate and severe groups according to the National Institutes of Health Stroke Scale(NIHSS)score at admission,and they were also divided into END and non-END groups based on the occurrence of END after intravenous thrombolysis.Clinical materials of ACI patients were collected;the expression level of serum AIM2 was measured by enzyme-linked immunosorbent assay(ELISA);the Logistic regression analysis was performed to identify the factors influencing END after intravenous thrombolysis in ACI patients;the receiver operating characteristic(ROC)curve was plot-ted to analyze the clinical performance of serum AIM2 expression level in predicting END after intravenous thrombolysis in ACI patients.Results The serum AIM2 expression level in the ACI group and the control group was(58.29±5.97)and(36.81±3.03)ng/mL respectively,with a significant be-tween-group difference(t=43.23,P＜0.05).The serum AIM2 expression level gradually in-creased in the mild,moderate and severe groups,with significant differences between each pair of groups(P＜0.01).The serum AIM2 expression level in ACI patients was positively correlated with the NIHSS score(r=0.941,P＜0.01).The NIHSS score,time from admission to thrombolysis,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,and AIM2 level in the END group were significantly higher or longer than those in the non-END group(P＜0.05).The results of mul-tivariate Logistic regression analysis showed that NIHSS score(OR=3.871,P＜0.001),time from admission to thrombolysis(OR=2.885,P=0.002),LDL-C(OR=3.118,P＜0.001)and AIM2(OR=3.761,P＜0.001)were influencing factors for END after intravenous thrombolysis in ACI patients.ROC curve showed that the area under the curve(AUC)for predicting END after in-travenous thrombolysis based on the serum AIM2 expression level at admission in ACI patients was 0.911;when the cut-off value of AIM2 was 66.56 ng/mL,the diagnostic sensitivity and specificity were 91.23％and 90.15％,respectively.Conclusion The expression level of serum AIM2 is sig-nificantly increased in ACI patients,and AIM2 expression level has certain advantages in predicting END after intravenous thrombolysis in ACI patients.