ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.

Objective:To observe the clinical progression of low-risk papillary thyroid microcarcinoma（LR-PTMC）, analyze the influencing factors of its oncological outcomes, and explore the feasibility of active surveillance（AS） of LR-PTMC. Methods:This study adopted a prospective observational research design. A total of 85 subjects diagnosed with LR-PTMC during health checkup in Health Management Center of our hospital from March 2021 to October 2022 were enrolled as the research subjects, for at least 2 years of AS follow-up observation. The clinical progress and oncological outcomes were recorded, disease progression was defined as any increase in nodule diameter ≥3 mm or the appearance of new lesions or lymph node metastasis or distant metastasis, and the oncological outcome was use disease progression defining. Cox proportional hazards regression model was used to analyze the influencing factors of oncological outcomes in LR-PTMC patients. Results:A total of 85 LR-PTMC patients who underwent physical examinations were included in this study. The median follow-up time was 2 years, and a total of 23 patients（27.06%） experienced disease progression. Among them, 18 patients（21.18%） had enlarged lesions（any nodule diameter increased by ≥3 mm）, and 5 patients（5.88%） had abnormal or metastatic cervical lymph nodes. The 2-year cumulative disease progression rate was 9.41%. The incidence age of LR-PTMC patients was younger, with a higher proportion of ≤45 years old. The proportion of baseline nodules with a maximum diameter greater than 5 mm is higher, and the proportion of baseline TPO Ab positivity was higher. Ultrasound showed a higher proportion of microcalcifications compared to the non progression group, and the differences were statistically significant（all P<0.05）. Multivariate Cox proportional hazards regression analysis showed that age of onset ≤45 years RR 95% CI 1.052（1.018-1.088） and ultrasound showing microcalcifications RR 95% CI 3.361（1.379-8.194） were independent risk factors affecting disease progression during AS in LR-PTMC patients（P<0.05）. Conclusion:Most LR-PTMC patients maintain stable lesion size and low lymph node metastasis rate during the AS process, with good oncological outcomes in the short term. AS can be considered as a safe and effective alternative to surgical treatment for LR-PTMC patients. But for patients with onset age ≤45 years and microcalcifications, the follow-up interval can be shortened for close observation.
Humans ; Thyroid Neoplasms/pathology* ; Disease Progression ; Prospective Studies ; Carcinoma, Papillary/pathology* ; Female ; Male ; Middle Aged ; Adult ; Watchful Waiting ; Lymphatic Metastasis ; Proportional Hazards Models ; Risk Factors

Objective To explore the regulatory effect of Lingzhu Granules on the PI3K/Akt signaling pathway in the rats with polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods Fe-male Sprague-Dawley(SD)rats aged 3 weeks d old were selected to establish the model by using the DHEA method.The intervention treatment was administered by different doses of Lingzhu Granules and the homeostasis model as-sessment of insulin resistance(HOMA-IR)was calculated.The relative expression levels of PI3K,Akt,GSK-3β and GLUT4 mRNA in the ovaries was detected by RT-PCR.The expression levels of PI3K and Akt were detected by Western blot.Results Compared with the model control group,the rat body weight in the medium and high doses Lingzhu Granules groups was significantly reduced(P＜0.05).The fasting blood glucose,fasting insulin and HOMA-IR index in the Lingzhu Granules low,medium and high doses groups were significantly lower than those in the model control group,and the differences were statistically significant(P＜0.01).The mRNA relative expression levels of PI3K,Akt,GSK-3β and GLUT4 in the Lingzhu Granules medium and high doses groups all were higher than those in the model control group(P＜0.05).The relative expression levels of PI3K and Akt in the ovarian tissue in the Lingzhu Granules low,medium and high doses groups were higher than those in the model control group,and the differences were statistically significant(P＜0.05).Conclusion Lingzhu Granules could effectively improve the insulin resistance status of PCOS rats by enhancing the synthesis of PI3K and Akt.

Objective To analyze the causes of infection and hemorrhage in patients with malignant obstructive jaundice(MOJ)after ultrasound-guided percutaneous transhepatic biliary drainage(PTBD).Methods A total of 420 patients with MOJ after PTBD in The Third Affiliated Hospital of Naval Medical University from Jun.2023 to Sep.2024 were enrolled,and their condition after PTBD,medical histories,preoperative examinations,and other clinical data were retrospectively analyzed.Univariate and multivariate logistic regression analyses were performed to explore the risk factors for postoperative infection and hemorrhage,and receiver operating characteristic(ROC)curves were plotted.Results Univariate logistic regression analysis showed that ascites,diuretics use,repeated punctures,hepatitis B virus(HBV)DNA and preoperative hemoglobin(Hb)levels,and neutrophil count(NE)were associated with infection after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that ascites,diuretic use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were the independent risk factors for infection after PTBD(all P＜0.05).Six factors including ascites,diuretics use,repeated punctures,HBV DNA and preoperative Hb levels,and NE were used to establish a prediction model.The area under the ROC curve of the model for predicting infection after PTBD was 83.1％(95％confidence interval[CI]75.5％-90.7％,P＜0.001).Univariate logistic regression analysis showed that liver tissue inflammation,ascites,preoperative peritoneal drainage,diuretics use,preoperative Hb and prealbumin(PA)levels were related to bleeding after PTBD(all P＜0.05).Multivariate logistic regression analysis showed that preoperative Hb and PA levels were independent risk factors for bleeding after PTBD.Preoperative Hb and PA levels were included to establish the prediction model.The area under the curve value for predicting bleeding after PTBD was 86.3％(95％CI 80.8％-91.9％,P＜0.001).Conclusion The prediction model for infection and hemorrhage after PTBD can facilitate early preventivon and intervention measures,thereby improving surgical safety.

Objective To explore the effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on the postoperative nausea and vomiting after thyroidectomy under general an-esthesia.Methods Seventy-two female patients underwent thyroidectomy,aged 18-50 years,ASA physical status Ⅰ or Ⅱ,were enrolled.The patients were assigned 1 ∶ 1 to two groups by permuted block randomization:the electrical stimulation group and the control group,36 patients in each group.Before an-esthesia induction,patients in both groups wore domestic transcutaneous electrical acupoint stimulation bracelets,and the electrodes were aimed at Neiguan acupoint.The electrical stimulation group started to stimulate Neiguan acupoint,and adjusted the proper intensity to make the patient feel tingling in the related area of the hand.When the bracelet was fixed firmly,turned it off.At the end of the operation,the bracelet was turned on with the stimulation intensity set before induction for 24 hours.Patients in the control group also wore the bracelet for 24 hours,but it was never turned on.The number of cases of postoperative nausea and vomiting(PONV)and the number of remedial cases of antiemetic drugs were recorded.Results Compared with the control group,the incidence of PONV and postoperative vomiting in the electrical stimula-tion group were significantly reduced within 24 hours after surgery(P＜0.05),and the differences were mainly in 1-6 hours after surgery(P＜0.05).There was no significant difference in the rate of remedial ca-ses of antiemetic drugs between the two groups at different time periods.Conclusion Transcutaneous electri-cal stimulation bracelet at Neiguan acupoint can effectively reduce the incidence of PONV within 24 hours after thyroidectomy.

Objective:To analyze the current prevalence of pre-diabetes (PDM) and its relationship with overweight and obesity in an adult health check-up population.Methods:This study was a cross-sectional and retrospective cohort study and was applied using whole-cluster random sampling method. A total of 491 379 adults who underwent health check-ups at the Health Management Centre of Sichuan Provincial People′s Hospital from January 2017 to July 2023 were selected to analyze the epidemiological characteristics of PDM and overweight-obesity, as well as the trend of change over time. A retrospective cohort study was conducted on 19 001 of the subjects who underwent≥3 health check-ups and did not have diabetes and PDM at baseline, and the relationships between body mass index, waist circumference and the risk for developing PDM were analyzed using Cox proportional risk regression models. And the dose-response relationship between body mass index, waist circumference and the risk for developing PDM was analyzed using restricted cubic spline regression (RCS).Results:Of the 491 379 cases included in the cross-sectional study, 275 084 were male and 216 295 were female, 163 158 cases were under 40 years old, and 328 221 cases were 40 years old and above; the total prevalence of PDM was 19.41% in 2017-2023, with an overall increasing trend. Of the 19 001 people included in the cohort study, a total of 2 487 (13.09%) new cases of PDM were identified at the end of follow-up. After adjusting for confounding factors, overweight ( HR=1.150, 95% CI: 1.047-1.263), obesity ( HR=1.335, 95% CI: 1.149-1.552) and abdominal obesity ( HR=1.218, 95% CI: 1.105-1.342) were risk factors for PDM. The risk of PDM rised with the increase of body mass index (>22.9 kg/m 2, Pnon-linear=0.973) and waist circumference (>80 cm, Pnon-linear=0.830), with a linear dose-response mode. In different gender and age groups, it was found the greater the body mass index (>24.1 kg/m 2 for men,>21.5 kg/m 2 for women;>23.3 kg/m 2 for age≥40 years,>24.1 kg/m 2 for age<40 years) and waist circumference (>85 cm for men, >73 cm for women; >82 cm for age ≥40 years, >85 cm for age <40 years), the higher the risk of PDM. Conclusions:The prevalence of PDM is on the rise in the adult health check-up population. To prevent PDM, it is necessary to control the body mass index and waist circumference to a lower level than the overweight and obesity standards.

Objective:To investigate the value of serum miR-145 and matrixmetallo proteinase-2 (MMP-2) levels in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy in triple-negative breast cancer.Methods:125 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in the Hospital from Jan. 2022 to Dec. 2023 were prospectively included as the study objects, and 130 healthy people matching the age of the case group who underwent physical examination in our hospital during the same period were included as the healthy control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the serum miR-145 level of all subjects. Serum MMP-2 levels were determined by enzyme-linked immunosorbent assay (ELISA). After neoadjuvant chemotherapy, patients were evaluated according to Miller-Payne (MP) grading criteria and divided into pCR group and non-PCR group.Results:The serum miR-145 level in patients with tertiary breast cancer was 1.49±0.27, which was significantly lower than that in healthy control group (2.79±0.49), with statistical significance ( t=20.33, P<0.001). The serum MMP-2 level in triple negative breast cancer patients was (153.07±38.36) ng/mL, which was significantly higher than that in healthy control group (84.38±12.63) ng/mL, and the difference was statistically significant ( t=26.13, P<0.001). After neoadjuvant chemotherapy, the serum miR-145 level in non-PCR patients before treatment was 1.36±0.21, which was significantly lower than that in pCR group (1.74±0.20), with statistical significance ( t=9.93, P<0.001). After neoadjuvant chemotherapy, the serum MMP-2 level in non-PCR patients before treatment was (169.57±30.45) ng/mL, which was significantly higher than that in pCR group (121.61±31.79) ng/mL, and the difference was statistically significant ( t=8.24, P<0.001). Pearson correlation analysis showed that there was a significant negative correlation between serum miR-145 and MMP-2 levels in patients with triple-negative breast cancer before treatment ( r=-0.47, P<0.001). ROC curve analysis results showed that serum miR-145 and MMP-2 levels before treatment predicted the sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 82.9% and 74.4%, 45.1% and 99.8%, respectively. The sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 84.1% and 88.4%, respectively. Conclusion:Serum miR-145 and MMP-2 levels are related to the efficacy of neoadjuvant chemotherapy in patients with triple-negative breast cancer, and the combined application of the two has certain predictive value.

Objective:To investigate the changes and clinical significance of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients undergoing breast cancer resection before and after radiotherapy.Methods:A total of 110 patients who were treated in our hospital from Jun. 2022 to Jun. 2023 for breast cancer and were to receive radiotherapy after surgery were prospectively selected as the observation group. Another 110 healthy volunteers were selected as the control group. The levels of VEGF and VCAM-1 in peripheral blood were compared, and the relationship among general data, tumor pathology and peripheral blood VEGF and VCAM-1 in the observation group was analyzed, and their relationship with disease and prognosis was analyzed.Results:VEGF and VCAM-1 levels in peripheral blood in the observation group were significantly higher ( F=1288.37, 309.32, P<0.05). The levels of VEGF and VCAM-1 in peripheral blood in the observation group were significantly lower than before radiotherapy ( t=23.45, 11.88, P<0.05). Before and after radiotherapy, VEGF and VCAM-1 levels in peripheral blood in the observation group were correlated with tumor stage, tumor differentiation degree and Ki-67 proliferation index ( ttumor stage=7.05, 2.14, 4.52, 4.76, ttumor differentiation degree=7.12, 6.62, 2.81, 3.15, tKi67 proliferation index=7.25, 4.60, 4.24, 2.48, P<0.05) ; Of 110 patients in the observation group, 73 were effective and 34 were ineffective. VEGF and VCAM-1 in effective group were significantly lower ( t=7.27, 9.08, P<0.05). Spearman correlation coefficient analysis showed that VEGF and VCAM-1 levels were significantly positively correlated with tumor stage and Ki67 proliferation index before and after radiotherapy ( rbefore radiotherapy=0.64, 0.54, 0.52, 0.52, rafter radiotherapy=0.32, 0.39, 0.37, 0.24, P<0.05), and negatively correlated with tumor differentiation degree ( rbefore radiotherapy=-0.41, -0.31, rafter radiotherapy=-0.68, -0.41, P<0.05). The prognostic value of combined radiotherapy was 0.801 [95% CI (0.714-0.871) ], which was higher than that of VEGF and VCAM-1 alone 0.690 [95% CI (0.5955-0.775) ] and 0.734 [95% CI (0.641-0.814) ]. Conclusion:The changes of VEGF and VCAM-1 levels in peripheral blood have a certain value in evaluating the short-term prognosis of patients undergoing breast cancer resection by radiotherapy.

Objective:To investigate the clinical efficacy, quality of life, safety, and medical expense of second-line treatment with ametinib versus first-line treatment with oxitinib in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Methods:This is a prospective clinical research study. A total of 72 patients with NSCLC who received second-line treatment with ametinib at the Affiliated Hospital of Jining Medical University from July 2020 to April 2022 were included in the amitinib group. Sixty-six patients with advanced NSCLC harboring EGFR mutations who underwent first-line treatment with ositinib were included in the ositinib group (one patient dropped out of the study, and sixty-five patients were included in the final analysis). There was no statistically significant difference in general information between the two groups. The ositinib group received ositinib treatment, while the amitinib group received amitinib treatment. After three courses of treatment, the short-term effectiveness was evaluated in both groups. The quality of life was compared before and after three courses of treatment in each group. Adverse reactions and average per-day hospital cost were compared between the two groups.Results:The disease control rate in the amitinib and oxitinib groups were 91.67% (66/72) and 90.77% (59/65), respectively, while the overall response rate was 43.06% (31/72) and 41.54% (27/65), respectively. The disease control rate and overall response rate did not differ significantly between the two groups (both P > 0.05). After treatment, the scores for physical well-being [(21.05 ± 4.18) points vs. (19.16 ± 3.95) points, t = 4.05], social/family well-being [(19.38 ± 2.65) points vs. (17.26 ± 2.28) points, t = 3.11], emotional well-being [(18.83 ± 3.07) points vs. (17.00 ± 2.86) points, t = 3.20], functional well-being [(22.02 ± 3.83) points vs. (20.14 ± 2.98) points, t = 3.83], and additional attention [(26.11 ± 5.00) points vs. (24.33 ± 4.30) points, t = 3.05] in the amitinib group were significantly higher than those in the oxitinib group (all P < 0.05). There was no significant difference in incidence rate of grade 3-4 adverse reactions between amitinib and oxitinib groups [6.94% (5/72) vs. 10.77% (7/65), P > 0.05]. Average per-day hospital cost in the amitinib group was significantly lower than that in the oxitinib group ( t = 4.83, P < 0.05). Conclusion:Second-line treatment with ametinib for advanced NSCLC harboring EGFR mutations can significantly enhance the quality of life and offer comparable short-term efficacy and safety to first-line treatment with oxitinib. Advantageously, its medical cost is relatively lower.