Objective:To analyze the effect and safety of tirofiban bridging combined with aspirin for anti-platelet therapy in patients with acute cerebral infarction (ACI) beyond the thrombolytic time window.Methods:Sixty patients with ACI treated in Beijing Royal Hospital from January 2021 to September 2022 were retrospectively analyzed. Among them, 30 cases were treated with tirofiban bridging aspirin as the observation group, while 30 cases were treated with aspirin alone as the control group. The total effective rate of clinical treatment, the degree of neurological deficit, the degree of disease outcome and the incidence of adverse reactions were compared between the two groups. The degree of neurological deficit was evaluated using the National Institutes of Health stroke scale (NIHSS), and the degree of disease outcome was evaluated using the modified Rankin scale (mRS).Results:The overall effective rate in the observation group was significantly higher than that in the control group: 93.3% (28/30) vs. 66.7% (20/30), with a statistically significant difference ( χ2 = 10.97, P<0.01). Before treatment, there was no statistically significant difference in NIHSS score between the two groups ( P>0.05). However, after treatment, the NIHSS score in the observation group was significantly lower than that in the control group: (2.83 ± 1.87) scores vs. (4.93 ± 3.05) scores, indicating a significant difference ( t = -3.21, P = 0.002). No significant difference was observed in mRS score between the two groups before treatment( P>0.05). After treatment, the observation group showed significantly lower mRS score compared to the control group: 2.00 (1.00, 2.00) scores vs. 3.00 (2.00, 4.00) scores ( P = 0.006). There was no statistical difference in the incidence of adverse reactions between the observation group and control groups ( P>0.05). Conclusions:Tirofiban bridging aspirin has stronger inhibitory effect on platelet activity than simple application of aspirin for ACI patients with ultra-thrombolytic window, which can rapidly improve the degree of neurological impairment and daily living ability of patients, and the incidence of adverse reactions has not increased significantly.

Objective:To research the mechanism of the regulation of homeobox B8(HOXB8)for lysine demethylase 6B(KDM6B)-mediated CCAAT/enhancer binding protein α(C/EBPα)axis on the metastasis of high-grade serous ovarian cancer(HGSOC),so as to provide references for the study of the pathogenesis of HGSOC patients.Methods:The tumor tissue samples and corresponding adjacent normal tissue samples of HGSOC patients admitted to Wuhan Hospital of Traditional Chinese and Western Medicine from June to December 2024 were selected,and cell lines SKOV3 and A2780 of ovarian cancer were collected.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was adopted to detect the mRNA levels of KDM6B in HGSOC tumor tissues and its corresponding adjacent tissues.Western blot assay and immunohistochemistry were adopted to detect the expressions of KDM6B protein in the tissue.The A2780 cells of ovarian cancer were divided into the oe-HOXB8 group that was transfected by the HOXB8 overexpression vector,and the oe-NCHOXB8 group with the negative control(NC)vector.The SKOV3 cells of ovarian cancer were divided into the si-HOXB8 group that was transfected by the HOXB8 small interference sequence,and the si-NCHOXB8 group with negative control sequence.The transfected KDM6B was divided into the si-KDM6B group with small interference sequence and the oe-KDM6B group transfected with overexpression vector.The co-transfection HOXB8 and(or)KDM6B,C/EBPα were divided into si-HOXB8+si-KDM6B group and si-HOXB8+si-C/EBPα group of small interference sequence.The chromatin immunoprecipitation-qPCR(ChIP-qPCR)and dual-luciferase reporter gene assay were used to verify the mechanism that HOXB8 transcript and regulate KDM6B in SKOV3 and A2780 cells of ovarian cancer.The effects of overexpression or silencing of HOXB8 in A2780 and SKOV3 cells on the proliferation,invasion,migration and KDM6B expression of ovarian cancer cells were detected.The effects of overexpression or silencing of KDM6B in SKOV3 cells on the trimethylation modification of lysine 27 at histone H3(H3K27me3)and the expression of C/EBPα were detected.The effects of silencing KDM6B and C/EBPα on HOXB8-induced cell proliferation,invasion and migration were analyzed through functional rescue experiments.Results:In tumor tissues,the mRNA and protein expression levels of KDM6B were 1.02±0.03 and 1.02±0.04,respectively,which were significantly higher than those in the adjacent tissues,and the differences were statistically significant(t=62.440,38.737,P<0.01).The optical density value of proliferation,invasion rate and migration rate of A2780 cells in the oe-HOXB8 group that was transfected by the HOXB8 overexpression vector were respectively(1.74±0.15),(89.71±6.60)%and(85.33%±7.02)%,which were significantly higher than those in the oe-NCHOXB8 group,and the differences were statistically significant(t=7.778,7.353,4.759,P<0.01).The optical density value of proliferation,invasion rate and migration rate of SKOV3 cells in the si-HOXB8 group were respectively(0.54±0.06),(47.23±3.41)%and(43.20±3.12)%,all of which were significantly lower than those in the si-NCHOXB8 group,and the differences were statistically significant(t=9.400,8.615,9.040,P<0.01).The optical density value of proliferation,invasion rate and migration rate of SKOV3 cells in the si-HOXB8+si-KDM6B group were(1.04±0.09),(73.11±4.98)%and(68.65±4.45)%,respectively,which were significantly higher than those in the si-HOXB8 group,and the differences were all statistically significant(t=6.875,6.852,7.562,P<0.01).The optical density value of proliferation,invasion rate and migration rate of SKOV3 cells in the si-HOXB8+si-C/EBPα group were respectively(0.97±0.07),(75.87±5.12)%and(70.59±4.81)%,all of which were significantly higher than those in the si-HOXB8 group,and the differences were all statistically significant(t=6.355,7.500,7.884,P<0.01).Conclusion:HOXB8 can inhibit the C/EBPα expression and promote the HGSOC metastasis by regulating and controlling H3K27me3 modification of KDM6B-mediated C/EBPα histone.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Ulcerative colitis(UC)is a chronic,progressive inflammatory bowel disease associated with an increased risk of color-ectal cancer.In recent years,traditional Chinese medicine(TCM)has been increasingly utilized in the treatment of UC,and its thera-peutic efficacy has gained widespread recognition.Nevertheless,several challenges remain in optimizing TCM's role in UC manage-ment,which hinder the full realization of its potential benefits.This paper reviews the current status of TCM in treating UC,identifies existing challenges,and proposes targeted strategies to promote the advancement of TCM in this field.

From 2019 to 2023, a total of 30.8602 million doses of non-National Immunization Program (non-NIP) vaccines were administered in Shaanxi Province, averaging 1 561 doses per 10 000 population. The annual administration of non-NIP vaccines increased from 4.359 1 million doses in 2019 to 7.858 2 million doses in 2023, with their proportional representation among all vaccines rising from 30.82% to 55.15%( χ2 trend=2 440 581.54, P<0.001). The administration rate per 10 000 population increased from 1 105 doses to 1 986 doses during this period( χ2 trend=373.10, P<0.001). Concurrently, the substitution rate of non-NIP vaccines for National Immunization Program vaccines rose from 4.94% in 2019 to 16.11% in 2023.

Objective:To explore the effect of learning stress on weight and the mediating effect abnormal eating behavior in junior high school students.Methods:By multi-stage stratified cluster sampling,2 686 junior high school students were selected and investigated the learning stress and abnormal eating behavior with the middle school students' learning stress questionnaire and the Chinese version of the Dutch eating behavior questionnaire(C-DEBQ).The height and weight of the students were measured and the body mass index(BMI)was calculat-ed.Bootstrap method was used to analyze the mediating effect by using Process 4.1 software.Results:The preva-lence of overweight and obesity among 2 686 junior high school students was 19.8％.The score of middle school students'learning stress questionnaire was(57.6±11.3),the score of restricted eating was(20.0±7.3),the score of emotional eating was(21.3±9.5),and the score of exogenous eating was(25.8±7.7).There was a positive correlation between learning stress,restricted eating,emotional eating,overweight and obesity(r=0.08-0.24,Ps＜0.001).In the relationship between learning stress and overweight and obesity,the total indirect effect coefficient of restrictive eating behavior and emotional eating behavior was 0.013,indicating a partial mediating effect(95％CI:0.010-0.015,0.001-0.002).Conclusion:Learning stress could directly or indirectly affect the weight of junior high school students through abnormal eating behavior,increasing the risk of overweight and obesity.

Objective: To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD). Methods: Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18. Results: Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05). Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.

Objective:To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance.Methods:A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People?s Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown.Results:The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)( P<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis ( P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer ( P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. Conclusions:The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.

From 2019 to 2023, a total of 30.8602 million doses of non-National Immunization Program (non-NIP) vaccines were administered in Shaanxi Province, averaging 1 561 doses per 10 000 population. The annual administration of non-NIP vaccines increased from 4.359 1 million doses in 2019 to 7.858 2 million doses in 2023, with their proportional representation among all vaccines rising from 30.82% to 55.15%( χ2 trend=2 440 581.54, P<0.001). The administration rate per 10 000 population increased from 1 105 doses to 1 986 doses during this period( χ2 trend=373.10, P<0.001). Concurrently, the substitution rate of non-NIP vaccines for National Immunization Program vaccines rose from 4.94% in 2019 to 16.11% in 2023.

Objective:To explore the effect of learning stress on weight and the mediating effect abnormal eating behavior in junior high school students.Methods:By multi-stage stratified cluster sampling,2 686 junior high school students were selected and investigated the learning stress and abnormal eating behavior with the middle school students' learning stress questionnaire and the Chinese version of the Dutch eating behavior questionnaire(C-DEBQ).The height and weight of the students were measured and the body mass index(BMI)was calculat-ed.Bootstrap method was used to analyze the mediating effect by using Process 4.1 software.Results:The preva-lence of overweight and obesity among 2 686 junior high school students was 19.8％.The score of middle school students'learning stress questionnaire was(57.6±11.3),the score of restricted eating was(20.0±7.3),the score of emotional eating was(21.3±9.5),and the score of exogenous eating was(25.8±7.7).There was a positive correlation between learning stress,restricted eating,emotional eating,overweight and obesity(r=0.08-0.24,Ps＜0.001).In the relationship between learning stress and overweight and obesity,the total indirect effect coefficient of restrictive eating behavior and emotional eating behavior was 0.013,indicating a partial mediating effect(95％CI:0.010-0.015,0.001-0.002).Conclusion:Learning stress could directly or indirectly affect the weight of junior high school students through abnormal eating behavior,increasing the risk of overweight and obesity.