Objective Investigate the expression level of discs large homolog associated protein 5(DLGAP5)in oral squamous cell carcinoma(OSCC)and analyze its effects on cell proliferation,migration,invasion capacity,and the Warburg effect.Methods Bioinformatics analysis was performed to identify the potential therapeutic targets for OSCC.A total of 72 OSCC tissue samples and 40 adjacent non-cancerous tissue samples collected in the First Affiliated Hospital of Shihezi University from 2013 to 2024 were included,and the clinical pathological and prognostic data were collected from patients.Immunohistochemistry assay was applied to detect the protein expression of DLGAP5,and its association with clinical pathological features was analyzed.Kaplan-Meier survival curve was plotted for survival analysis,and Cox regression model was employed to analyze the prognostic factors.The expression of DLGAP5 at mRNA and protein levels was detected in HOK,SCC-9,SCC-15,SCC-25,and CAL-27 cell lines with RT-qPCR and Western blotting,respectively.Four small interfering RNAs(siRNAs)were designed to target the DLGAP5 sequence,and then based on the transfection efficiency,the sequence with optimal silencing effect was selected for subsequent functional studies.After DLGAP5 was silenced in the CAL-27 and SCC-15 cells,Western blotting was applied to detect the expression of hexokinase 2(HK2)and enolase 1(ENO1),CCK-8,scratch healing and Transwell assays were conducted to assess cell proliferation,migration,and invasion capabilities,and glucose,lactate,and ATP detection kits were utilized to determine the glycolytic metabolic levels in OSCC cells.Results Bioinformatics analysis indicates that DLGAP5 is a potential key therapeutic target for OSCC.Experimental validation demonstrated that DLGAP5 was highly expressed in both OSCC tissues and cells(P<0.05).Analysis of clinical pathology and prognostic data revealed that DLGAP5 expression level was significantly correlated with tumor TNM stage,lymph node metastasis,and differentiation grade in OSCC patients,and high DLGAP5 expression was associated with poor prognosis(P<0.05).DLGAP5 silencing resulted in significantly reduced expression of HK2 and ENO1,markedly decreased levels of glycolytic metabolites(P<0.05),and notably declined cell proliferation,migration,and invasion capabilities(P<0.05).Conclusion DLGAP5 is highly expressed in OSCC.Silencing DLGAP5 may inhibit OSCC cell proliferation,migration,and invasion by indirectly regulating the Warburg effect,and the molecule is associated with poor prognosis in the OSCC patients.

Objective To investigate the predictive value of serum uric acid(UA),homocysteine(Hcy)and the product index of UA and Hcy in patients with stable coronary artery disease(SCAD).Methods A total of 783 patients with suspected coronary heart disease were collected,all of whom underwent coronary angiography.Patients were divided into coronary heart disease(CHD)group and non-coronary heart disease(NCHD)group.The CHD group was further divided into low score group(≤35 points)and high score group(>35 points)according to Gensini scores.Baseline data,blood lipids,Hcy,UA,left ventricular function ultrasound indicators,and comorbidities were collected.Logistic regression analysis was used to evaluate the risk factors associated with the onset of SCAD and severe coronary artery disease,while the Receiver Operating Characteristic(ROC)curve was conducted to assess the predictive efficacy of the product index of UA and Hcy,and related risk factors,for SCAD onset and severe coronary artery disease.Results 1.In CHD group,UA,Hcy and the product index of UA and Hcy were all higher than in the NCHD group(P<0.001);the high-score group had higher UA,Hcy and the product index of UA and Hcy than the low Gensini score group(P<0.001).2.Multivariate logistic regression analysis showed that female age,sex,body mass index(BMI),product index of UA and Hcy,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),type 2 diabetes mellitus(T2DM)and hypertension(HTN)were independent risk factors for SCAD(P<0.05).BMI,the product index of UA and Hcy,HDL-C,LDL-C and LVEF were independent risk factors for severe coronary artery disease(P<0.05).3.There was a positive correlation between UA and Hcy product index and Gensini scores(r=0.433,P<0.05).4.Receiver operating characteristic curve analysis showed that the product index of UA and Hcy and combined detection of coronary heart disease risk factors had predictive value for the occurrence of SCAD(P<0.05),and the predictive value of combined detection was higher(area under the curve 0.808);both the product index of UA and Hcy and the combined detection of coronary heart disease risk factors had predictive value for severe coronary artery lesions(P<0.05),with a higher predictive value for combined detection(area under the curve 0.771).Conclusion As an independent predictor of the risk of SCAD and severe coronary stenosis,the product index of UA and Hcy has a high predictive efficacy regarding disease risk and the severity of coronary artery in patients with SCAD.

Objective To evaluate the predictive value of changes in serum homocysteine(Hcy),high-density lipoprotein cholesterol(HDL-C),and the homocysteine-to-HDL-C ratio(HHR)for the incidence and short-term prognosis of patients with premature coronary heart disease(PCHD).Methods Between January 2022 and December 2023,301 patients with the suspected coronary heart disease(males≤55 years,females≤65 years)were retrospectively selected from the Department of Cardiology at the Third People's Hospital of Yunnan Province.All patients who underwent coronary angiography(CAG)were divided into the premature coronary heart disease(PCHD)group(n=98)and the non-coronary heart disease(NCHD)group(n=203).Patients with PCHD were followed up six months after the discharge and were further classified into the good prognosis group(n=55)and the poor prognosis group(n=43)based on the presence of worsening clinical symptoms such as chest tightness,chest pain,arrhythmias,heart failure,or death.Data collected included general patient information,blood lipid levels,Hcy levels,left ventricular function ultrasound indicators,and the presence of hypertension and type 2 diabetes.Results Hcy and HHR levels were significantly higher in the PCHD group compared to the NCHD group,while HDL-C levels were lower(P<0.001).In the poor prognosis group,Hcy and HHR levels were elevated,and HDL-C levels were reduced compared to the good prognosis group(P<0.001).The Hcy and HHR levels in the severe coronary artery stenosis group were markedly higher than those in the normal coronary artery group and the mild to the moderate stenosis group,with HDL-C levels being lower(P<0.001).Multivariate logistic regression analysis identified that male sex,HHR,Hcy,low-density lipoprotein cholesterol(LDL-C),and left ventricular ejection fraction(LVEF)were independent factors influencing premature coronary heart disease(P<0.05).HHR was found to be an independent risk factor for the poor short-term prognosis in PCHD.The analysis of the operating characteristic curve of the subjects showed that serum Hcy and HHR had the predictive value for the occurrence of PCHD(P<0.05),with HHR showing higher predictive value(area under the curve[AUC]=0.713).HHR also had the substantial predictive value for the short-term prognosis of PCHD(AUC=0.715).Conclusion Elevated HHR levels are associated with the severe coronary artery disease in patients with PCHD.HHR serves as a significant predictor for both the occurrence and short-term prognosis of PCHD.

The emerging and re-emerging arthropod-borne infectious diseases pose a serious threat to global public health security. Field and laboratory studies of arthropods of medical importance are essential and critical for the prevention and control of arthropod-borne infectious diseases. Various institutions or universities in China have been conducting research in the field or laboratory study of arthropods of medical importance, but up to 2023, it is still lacking detailed biosafety guidelines or recommendations that can guide the related work for arthropods of medical importance. In order to proactively address potential biosafety issues in the field or laboratory activities related to arthropods of medical importance, improve the standardization of arthropod biosafety classification, operations, and protection, and ensure the safety of practitioners, an expert consensus on the biosafety recommendation of arthropods of medical importance in field and laboratory has been developed, aiming to guide the future work of arthropods and ensure the national biosafety and biosecurity of China.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

Objective To explore the effects of multiple groups of acupoint pre-embedding thread on the autonomic nervous system and gastrointestinal function in patients undergoing gynecological laparo-scopic surgery under general anesthesia.Methods Sixty patients,aged 25-64 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were selected for laparoscopic gynecological surgery under general anesthesia.Patients were divided into two groups using a random number table method:control group(group C)and acupoint thread embedding group(group M),30 patients in each group.Patients in group M received thread embedding at 10 acupoints in 5 groups,including Neiguan,Sanyinjiao,Geshu,Jueyin,and Weishu on the day before surgery.Patients in group C did not undergo thread embedding at acupoints before surgery.The HR,MAP,normalized unit of low frequency(LF),normalized unit of high frequency(HF)and LF/HF were recorded at 5 minutes before anesthesia induction,immediately after tracheal intu-bation,immediately after establishing pneumoperitoneum,10,20,and 30 minutes after pneumoperitoneum,and when tracheal intubation was removed.Motilin and gastrin concentrations in serum were measured on the day before surgery and 24 hours after surgery.The time of first postoperative exhaust and defecation,as well as the occurrence of nausea and vomiting within 48 hours after surgery were recorded.Results Compared with group C,the HR was significantly lower,and the MAP,the LF and LF/HF in group M were significant-ly reduced at 10,20,and 30 minutes after pneumoperitoneum,while HF was significantly increased(P＜0.05).The first postoperative time of exhaust and defecation in group M was significantly shortened(P＜0.05),and the incidence of nausea and vomiting within 24 hours after surgery was significantly reduced(P＜0.05).The concentrations of motilin and gastrin in serum of group M were significantly increased 24 hours after surgery(P＜0.05).Conclusion The combination of acupoints and pre-embedding thread can regu-late the autonomic nervous function of patients undergoing gynecological laparoscopic surgery under general anesthesia,which is beneficial for the recovery of postoperative gastrointestinal function and improves the quality of rehabilitation.

Objective : To explore differential expression of insulin like growth factor 1( IGF1) in oral squamous cell carcinoma (OSCC) tissues and cells , and to analyze its clinical significance of IGF1 . Methods : The protein expression of IGF1 was detected in 115 OSCC tissues (OSCC group) and 74 normal tissues (normal group) using immunohistochemical technique , and the relationship with the clinicopathological factors and prognosis of OSCC was analyzed. The IGF1 protein and mRNA levels in HOK and OSCC cell lines ( CAL⁃27 , TCA⁃8113 , SCC⁃15 and SCC⁃25) were detected by Western blot and qRT⁃PCR. Results : The high expression rate of IGF1 in OSCC group was 72. 17% , which was significantly higher than that in normal group (2. 70% ) ( P < 0. 001) . The proportion under ROC curve (AUC) of OSCC diagnosed by IGF1 was 0. 81 , the sensitivity was 0. 73 , and the specificity was 0. 82. The expression of IGF1 was related to the degree of differentiation , T stage and depth of invasion (P = 0. 03 , P = 0. 02 , P = 0. 02) , but not to gender, age , N stage , TNM stage , smoking , alcohol consumption , or HPV infection (P > 0. 05) . Kaplan⁃Meier and COX regression analysis showed that the high expression of IGF1 , the degree of differentiation , the T stage and the depth of infiltration were the related factors affecting the prognosis of patients (P < 0. 01 , P = 0. 04 , P = 0. 03 , P = 0. 04) . COX multivariate indicated that high expression of IGF1 was an independent factor affecting the prognosis of patients ( P = 0. 01) . Western blot and qRT⁃PCR results indicated that the expression of IGF1 in OSCC cell lines was higher than that in HOK (P < 0. 05) . Conclusion IGF1 can be a potential diagnostic and poor prognostic marker in oral squamous cell carcinoma.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective : To investigate the expression and prognosis of urokinase plasminogen activator (PLAU) and v-akt murine thymoma viral oncogene homolog 1 (AKT1) in oral squamous cell carcinoma ( OSCC) and normal tis- sues and the correlation of PLAU and AKT1 in OSCC tissues． Methods : The expression levels of PLAU and AKT1 in 70 cases of oral squamous cell carcinoma and 50 cases of normal tissues were detected by immunohistochemical method，and the correlation between PLAU and AKT1 expression and clinicopathological features and prognosis as well as the correlation between PLAU and AKT1 expression in OSCC tissues was analyzed，and the results were fur- ther verified by bioinformatics database. Results : The expression of PLAU and AKT1 in OSCC tissues was higher than that in normal tissues (P＜0. 05) ，Kaplan-Meier analysis showed that patients with low PLAU and AKT1 ex- pression had longer survival time than those with high AKT1 expression (P＜0. 05) ，Spearman rank sum correlation test showed that there was a strong correlation between PLAU and AKT1 expression in OSCC tissues (r = 0. 357，P ＜0. 05) ，GEPIA bioinformatics database analysis results are consistent with experimental results． Conclusion PLAU and AKT1 are highly expressed in OSCC tissues and are associated with poor prognosis of patients．There is a correlation between PLAU and AKT1 in OSCC tissues.