Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Objective:To understand the use of post-exposure prophylaxis (PEP) and analyze related factors among men who have sex with men (MSM) in Qingdao, and provide a reference for the AIDS prevention and control in this population.Methods:A cross-sectional survey conducted from April 2022 to February 2023. Relying on MSM social groups in Qingdao, a snowball sampling method was applied to recruit research subjects who met the inclusion criteria of age &ge;18 years old, having had homosexual anal or oral sex in the past six months, and HIV-negative or infection status unknown. The sample size was estimated at 566. Data on demographic characteristics, sexual behavior characteristics, PEP use, and others of the research subjects was collected through on-site questionnaires. The logistic regression model was used to analyze the factors associated with using PEP.Results:A total of 811 participants were recruited, mainly aged 25-34 (53.6%, 435/811), unmarried (74.7%, 606/811), with an average monthly income of &ge;5 000 yuan (52.2%, 423/811), and having lived in Qingdao for &ge;10 years (75.6%, 613/811). The proportion of those who knew the HIV status of their sexual partners in the last six months was 67.1% (544/811), and those with HIV-positive partners were 3.6% (29/811). In the last six months, the proportion of participants who had group sex (86.4%, 701/811), unprotected anal sex (98.2%, 796/811), and use of club drugs (80.3%, 651/811) was high. Moreover, 28.4% (230/811) had used PEP. The multivariate logistic regression analysis showed that the factors related to the use of PEP included divorced or widowed (a OR=5.46,95% CI:1.96-15.17), average monthly income &ge;5 000 yuan (a OR=2.04,95% CI:1.44-2.89), same-sex sexual orientation (a OR=0.40,95% CI:0.22-0.71), having HIV-positive sexual partners in the last six months (a OR=2.54,95% CI:1.13-5.71) and having been tested for HIV &ge;3 times in the last six months (a OR=1.46,95% CI:1.04-2.06). Conclusions:The prevalence of risk behaviors among MSM in Qingdao was high, and the use of PEP was low. In the future, it is essential to increase HIV/AIDS prevention education among MSM, promote MSM to know the HIV status of their sexual partners, and reduce the prevalence of risk behaviors among this population. Additionally, explore medical insurance reimbursement plans for PEP to reduce utilization costs and promote the use of PEP by MSM after HIV exposure occurs as soon as possible.

Objective:To explore the relationship between serum levels of transforming growth factor- β1 (TGF- β1), vascular endothelial growth factor (VEGF) and tumor markers and local recurrence after breast-conserving surgery in patients with breast cancer. Methods:104 patients with breast cancer who underwent breast-conserving surgery in Xi’ an Central Hospital from Jan. 2020 to Dec. 2022 were selected and followed up for 1 year after surgery. According to the occurrence of local recurrence, they were divided into recurrence group ( n=16) and non-recurrence group ( n=88). The levels of serum TGF- β1, VEGF and tumor markers [carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) ] were compared between the two groups of patients. Univariate and multivariate Logistic regression analyses were used to analyze the influencing factors of local recurrence after breast-conserving surgery. Receiver operating characteristic (ROC) curve was applied to analyze the predictive value of TGF- β1, VEGF, CA125 and CEA on local recurrence after breast-conserving surgery. Results:The levels of VEGF, TGF- β1, CAl25 and CEA in recurrence group [ (358.83±38.00) ng/L, (849.90±74.19) U/mL, (18.34±1.61) ng/L and (40.20±5.64) ng/mL] were higher than those of (296.05±39.57) ng/L (742.85±79.96) ng/L, (14.97±1.66) U/mL and (32.79±4.72) ng/mL in non-recurrence group (all P<0.05). Lymph node metastasis, postoperative adjuvant therapy, tumor diameter and TNM staging were independent risk factors of local recurrence after breast-conserving surgery (all P<0.05). The areas under the ROC curves (AUCs) of serum VEGF, TGF- β1, CAl25 and CEA in predicting local recurrence after breast-conserving surgery were 0.847, 0.834, 0.925 and 0.935 respectively. The AUC of CEA was the largest, with sensitivity of 85.23% and specificity of 100% (all P<0.05) . Conclusions:The levels of TGF- β1, VEGF, CAl25 and CEA in patients with local recurrence after breast-conserving surgery are increased, and their levels are more effective in predicting local recurrence after breast-conserving surgery. Local recurrence after breast-conserving surgery is also affected by lymph node metastasis, postoperative adjuvant therapy, tumor diameter and TNM staging.

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC₅₀ = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (t _1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC₅₀ = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH₂-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC₅₀ = 1.8-349 nmol/L). The best compound 5t in this collection (EC₅₀ = 1.8 nmol/L, CC₅₀ = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of 5t was also significantly improved (t _1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (t _1/2 = 14.6 min). Also, 5t possessed good stability in both human and monkey plasma. No significant in vitro inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of 5t as a drug candidate.

As a common psychiatric disorder, the etiology and pathogenesis of depression are complex and not yet fully elucidated.The diagnosis of depression mainly depends on the patients’ medical history, clinical symptoms and related examinations.Identification of biomarkers will provide important clues for the specific diagnosis and targeted treatment of depression.In addition to the widely recognized neurotransmitter dysregulation, hypothalamus-pituitary-adrenal axis hyperactivity, neuroplasticity, and neuro-inflammation theory, oxidative stress is also involved in the pathogenesis of depression in multiple ways.Many studies showed that the heat shock protein 70(HSP70)levels will increase in early stage to cope with the stress in patients with depression.However, lower HSP70 levels are often correlated with more severe depressive symptoms.HSP70 may be involved in depression through multiple pathways of oxidative stress, glucocorticoid receptors, neuroinflammation and neuroplasticity.Furthermore, increasing HSP70 expression results in significant improvement in depression-like behavior in animals.Thus, HSP70 possesses potential value as an early warning marker for depression as well as a therapeutic target.

Objective:To understand and analyze the incidence of HIV infection in club drug abusers among men who have sex with men (MSM) in Qingdao and provide a reference for the prevention and intervention of this population.Methods:From March 2017 to July 2022, club drug abusers among MSM who are HIV-negative were recruited by snowball sampling of MSM social organizations in Qingdao, a prospective cohort was established, and a follow-up survey was conducted every six months, with the sample size estimated to be 436. The survey contents included demographic characteristics, sexual characteristics, AIDS knowledge awareness, club drug abuse, HIV testing, and other information. HIV infection was the outcome-dependent variable, and the interval between the recruitment into the cohort and the HIV infection was the time-dependent variable. Cox proportional hazards regression analysis was conducted to identify the related factors for HIV infection.Results:A total of 987 participants of club drug abusers among MSM were recruited during the baseline survey and 826 eligible participants were enrolled in this cohort. A total of 46 HIV infection cases were found, and the cumulative follow-up time was 1 960.68 person-years. The incidence of HIV infection was 2.35/100 person-years. The multivariate Cox regression analysis showed that <30 (a HR=3.04, 95% CI: 1.62-5.71) non-Shandong residents (a HR=2.29,95% CI:1.20-4.39) found their partners through offline (a HR=4.62,95% CI:2.05-10.41), homosexual sexual partners >4 (a HR=3.06,95% CI:1.59-5.88), condom broken during sex (a HR=2.24,95% CI:1.21-4.17) and hemorrhage sexual intercourse (a HR=2.56,95% CI:1.31-5.03) were significantly associated with HIV infection in this cohort. Conclusions:The incidence of HIV infection in club drug abusers among MSM in Qingdao is generally low, but knowledge and practice have separated, and the risk of HIV infection is high. The related factors of HIV infection included younger age, non-Shandong residents, finding their partners offline, multiple sexual partners, condom break during sex, and hemorrhage sexual intercourse; HIV-related behavioral intervention should be strengthened.

Objective:To investigate the current situation of critical thinking ability of nurses in Catheterization Room in China, and analyze its influencing factors, so as to provide reference for improving the critical thinking ability of nurses in Catheterization Room.Methods:In July 2020, the catheterization nurses from 154 hospitals, including Class Ⅲ Grade A, Class Ⅲ Grade B and Class Ⅱ Grade A, in 28 provincial capital cities of China were investigated with general information questionnaire and Chinese Critical Thinking Disposition Inventory (CTDI-CV) , by convenience sampling method. 422 questionnaires were collected in this survey, 408 were valid, and the effective rate was 96.68%.Results:The total score of critical thinking ability of the 408 catheterization nurses was (247.92±33.77) , which was at a low level as a whole. There were 361 nurses (88.48%) without positive critical thinking, 42 (10.29%) with positive critical thinking, and 5 (1.23%) with strong positive critical thinking. Binary Logistic regression analysis showed that nurse level, education background, professional title and position were the main influencing factors of critical thinking ability of nurses in Catheterization Room ( P<0.05) . Conclusions:The critical thinking attitude of nurses in Catheterization Room is generally negative, which is far from positive, and needs to be further improved. The nursing department should give more tendentious policies and support to the nurses in the Catheterization Room. At the same time, the nursing managers in the Catheterization Room should actively take measures to improve the critical thinking ability of nurses.

Objective:To evaluate the efficacy of somatosensory evoked potential (SEP) monitoring for prevention of deep venous thrombosis (DVT) in lower extremity of patients undergoing spinal surgery.Methods:A total of 120 patients of both sexes, aged 40-70 yr, of American Society of Anesthesiologists physical status ⅠorⅡ, without impairment of coagulation function, undergoing posterior lumbar interbody fusion, were selected and divided into 3 groups ( n=40 each) using the random number table method and envelope method: basic preventive measure group (group A), compression stocking group (group B) and SEP monitoring group (group C). In group B, elastic stockings were worn at 1 h before surgery.SEP monitoring was performed during surgery, and the intensity of current stimulation was 25 mA in group C. The flow velocity of popliteal vein in both lower extremities was measured using color Doppler ultrasound apparatus during surgery.Venous blood samples were taken to measure plasma D-dimer concentrations at 1 day before surgery, at the end of surgery and at 24 h after surgery.The DVT developed in lower extremities was diagnosed by ultrasound method during surgery and within 24 h after surgery. Results:Compared with A and B groups, the blood flow velocity of popliteal vein was significantly increased, and the plasma D-dimer concentration and incidence of DVT developed in lower extremity during surgery were decreased in group C ( P<0.05). Conclusion:SEP monitoring can effectively prevent the occurrence of DVT in lower extremity while it is used as an electrophysiological monitoring of the spinal cord in patients undergoing spinal surgery.

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) loci polymorphism of Yersinia pestis and its area distribution in Gansu province. Methods:A total of 203 strains of Yersinia pestis isolated from 1962 to 2014 were selected for the culture and extraction of DNA. Three pairs of CRISPR primers were used to amplify the strain DNA by PCR, and the PCR products were sequenced. The groups and genotypes of strains were determined according to the spacer and spacer arrangement of CRISPR loci in the strain. Cluster analysis was done by using the software BioNumerics 5.10. Results:A total of 16 spacers, including 9 species of YPa loci, 4 species of YPb loci and 3 species of YPc loci, were found in the 203 strains of Yersinia pestis. A new spacer of a1′ was found. The 203 strains were divided into 5 CRISPR genotypes and classified into 5 CRISPR clusters (Cb2, Ca7, Ca7′, CaΔ5′ and Ca35′). Each cluster showed significant area-specific characteristics, Cb2 was mainly distributed in Huining country and Pingchuan district, Ca7 was mainly found in Aksai Kazak autonomous country, Ca7′ was mainly found in Xiahe country, Ca35′ was mainly found in Subei Mongolia autonomous county and Yumen city and CaΔ5′ was mainly distributed in Sunan Yugur autonomous county. Conclusions:The strains from different plague foci in Gansu were distinguished by CRISPR, all kinds of clusters showed the obvious area specific characteristics. It is important to study the evolution of Yersinia pestis in Gansu and trace the molecular biology origin of human plague.