Purpose To investigate the expression of fork-head box protein A1(FOXA1)in esophageal squamous cell car-cinoma(ESCC)and its association with clinicopathologic char-acteristics and prognosis.Methods Immunohistochemistry was used to detect FOXA1 protein expression in 532 cases of esopha-geal squamous cell carcinoma.The correlation between FOXA1 protein expression and clinicopathologic features and prognosis of patients was analyzed.Results In 532 cases of esophageal squamous cell carcinoma,183 cases overexpressed FOXA1 pro-tein(34.4％).FOXA1 overexpression was associated with ES-CC vascular infiltration(P=0.032),poorly differentiation(P=0.032),and tumor size(P＜0.001).The overall survival(OS)and disease free survival(DFS)of patients with stage Ⅰ+Ⅱ esophageal squamous cell carcinoma with high FOXA1 ex-pression tended to be poor(OS:P=0.094;DFS:P=0.107).In ESCC patients with survival longer than 24 months,the high FOXA1 expression group had significantly shorter OS and DFS(OS:P=0.048;DFS:P=0.047).Multivariate survival anal-ysis showed that the depth of tumor invasion was an independent prognostic factor affecting the prognosis of esophageal squamous cell carcinoma.Conclusion FOXA1 is overexpressed in e-sophageal squamous cell carcinoma,and its high expression is related to tumor size,vascular infiltration and poorly differentia-tion.Patients with high FOXA1 expression tended to have poor prognosis in OS and DFS.When OS and DFS≥24 months,high FOXA1 expression may be used as a reference indicator for poor prognosis in ESCC patients.

Objective: To investigate the correlation between campus bullying and suicidal tendency symptoms comorbidity with addictive behavior among middle and high school students in Hainan Province, so as to provide a theoretical basis for health education and behavioral intervention in schools. Methods: In July 2023, an anonymous questionnaire survey was conducted among 6 654 middle and high school students in Hainan Province, selected by probability proportional sampling and stratified cluster random sampling method. Campus bullying, suicidal tendency and addictive behavior were determined according to the relevant items in the questionnaire on health related behaviors of Chinese students health status and influencing factors questionnaire, and self designed questionnaire. The co occurrence of campus bullying and suicidal tendency among students was analyzed. The binary Logistic regression method was used to analyze the correlation between the co occurrence of campus bullying and suicidal tendency and the addictive behavior of middle school students. Results: The report rate of campus bullying among middle and high school students in Hainan Province was 28.48%, the suicidal tendency was 15.25%, and the co occurrence of campus bullying and suicidal tendency was 8.00%. The results of Logistic regression analysis showed that middle school students and left behind students were prone to campus bullying and suicide tendency ( OR =1.55, 1.52, P <0.05), while Internet addiction, gambling and current smoking showed significant positive correlation with comorbidity of campus bullying and suicide tendency ( OR =3.14, 2.18, 2.07, P < 0.05 ). Conclusions Middle and high school students with addictive behavior have a higher possibility of comorbidity of campus bullying and suicidal tendency. The comprehensive intervention of addictive behavior can reduce the incidence of co occurrence of campus bullying and suicidal tendency, so as to improve health and wellbeing of middle school students.

Objective To explore the expression and clinical significance of Yes-associated protein 1(YAP1)in esophageal squamous cell carcinoma.Methods Immunohistochemical method was used to detect YAP1 expression in 439 cases of esophageal squamous cell carcinoma.The differences of YAP1 expression and clinical parameters were analyzed between YAP1 positive group and YAP1 negative group.Kaplan-Meier curve was used to analyze the influence of YAP1 expression on survival of patients.Results The positive rate of YAP1 in esophageal squamous cell carcinoma was 30.52% .The tumor invasion was deeper in YAP1 positive group(P＜0.001).Kaplan-Meier survival analysis showed that YAP1 positive patients had longer disease-free survival(DFS)and overall survival(OS)among patients surviving longer than 30 months(P＜0.05).The multivariate Cox regression analysis showed that the invasion depth of tumor was an independent factor affecting DFS(HR=1.371,95% CI 0.993-1.894,P=0.035)and OS(HR=1.489,95% CI 1.066-2.080,P=0.020).Conclusions YAP1 has a certain percentage of positive rate in esophageal squamous cell carcinoma;for patients with survival longer than 30 months,YAP1 positive indicates a better prognosis.

This paper summarized professor WANG Xinlu's experience in clinical application of hongjingtian （Radix et Rhizoma Rhodiolae Crenulatae）. It is believed that hongjingtian is good at boosting qi and supplementing deficiency， moving qi and resolving constraint， invigorating blood and unblocking vessels， which can be widely used in various diseases caused by qi-blood disorders such as qi deficiency， qi constraint， and blood stasis. Hongjingtian is commonly used with jixueteng （Caulis Spatholobi） to boost qi and nourish blood， invigorate blood and unblock vessels， and together with yuzhizi （Fructus Akebiae） to regulate qi and invigorate blood， dissolve stasis and dissipate masses. According to the specific symptoms， hongjingtian can be flexibly combined with other medicinal herbs to prepare different experienced formulas， such as self-made Sanhong Yangxin Decoction （三红养心汤） for palpitation with qi deficiency and blood stasis syndrome， self-made Anfei Dingchuan Decoction （安肺定喘汤） for exacerbation of asthma with deficiency syndrome， self-made Honghu Jieyu Decoction （红胡解郁汤） for constraint syndrome of qi constraint and blood stasis， and self-made Shexue Chudian Decoction （摄血除癜汤） for idiopathic thrombocytopenic purpura with qi deficiency failing to contain syndrome. For severe cases of coronavirus disease 2019 （COVID-19） with qi-yin desertion syndrome， hongjingtian is commonly used together with modified Shengmai Powder and Tingli Dazao Xiefei Decoction （生脉散合葶苈大枣泻肺汤）， and for those with yang qi external desertion syndrome， hongjingtian combined with shanyurou （Fructus Corni） and Shenfu Decoction （参附汤） is recommended. Moreover， long COVID-19 with healthy qi deficiency and pathogen lingering syndrome can be treated with self-made Xinguan Fuyu Decoction （新冠复愈汤）.

AIM:To investigate the effect of melatonin(MEL)on the depression behavior in mice induced by chronic restraint stress(CRS).METHODS:Forty-eight SPF-grade male C57BL/6J mice were randomly divided into con-trol group(n=12)and CRS group(n=36).The mice in CRS group were further divided into 3 groups(n=12):CRS+vehi-cle group,CRS+fluoxetine(FLX)group,and CRS+MEL group.Mouse depression model was established by the CRS method for 14 d,and then the depression-like behaviors were observed for modeling validation.After 14 d of drug interven-tion combined with CRS,the behaviors were detected again.Nissl staining,RT-qPCR,Western blot and immunofluores-cence staining were performed in mouse brain tissues.RESULTS:Compared with control group,the weight changes of the mice in CRS group were significantly lowered,the immobility time of forced swimming and tail suspension tests was sig-nificantly increased,the consumption rate of sugar water decreased significantly,and the central time and movement dis-tance in open-field test decreased significantly(P＜0.01).Compared with CRS+vehicle group,the depression-like behaviors induced by CRS were successfully reversed by the drugs in both CRS+FLX and CRS+MEL groups.Furthermore,com-pared with CRS+vehicle group,the mRNA levels of brain-derived neurotrophic factor(BDNF),extracellular signal-regulated kinase(ERK)and cAMP response element-binding protein(CREB),and the protein levels of BDNF,phosphorylated ERK1/2 and CREB were increased significantly in both CRS+FLX and CRS+MEL groups(P＜0.01).The results of Nissl staining showed that the neurons in CRS+vehicle group were irregularly arranged,and the number of Nissl bodies was de-creased(P＜0.01).The neuron status and number of Nissl bodies in both CRS+FLX and CRS+MEL groups were signifi-cantly improved(P＜0.01).Immunofluorescence staining showed that the number of c-Fos-positive cells in the frontal cor-tex and hippocampal CA1 region of the mice in CRS+vehicle group was significantly larger than that in control group(P＜0.01).Conversely,the number of c-Fos-positive cells in CRS+FLX and CRS+MEL groups was significantly smaller than that in CRS+vehicle group(P＜0.01).CONCLUSION:Melatonin can significantly alleviate depression-like behavior in-duced by CRS in mice,which may be related to the activation of BDNF-ERK-CREB signaling pathway.

For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy combined with surgery has become the standard treatment schedule. The application of immunotherapy, represented by programmed death-1 and programmed death-ligand 1 inhibitors, has injected new vitality into neoadjuvant therapy for ESCC. At present, a large number of clinical trials are being carried out and explored, which brings new challenges to the diagnosis of clinical pathologists. Combined with the latest researches at home and abroad and clinical diagnosis problems, the authors summarize the relevant problems and progress of pathological evaluation before and after neoadjuvant immunotherapy from the perspective of pathology, in order to improve the level of clinical pathological diagnosis and provide reference for further optimizing the comprehensive treat-ment strategy.

Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.

Breast cancer is the most common malignant tumor in women. The key to the prognosis of breast cancer lies in early diagnosis and early treatment.At present, the early diagnosis of breast cancer mainly relies on imaging methods, and there has been a lack of clinical methods for early diagnosis of it.Exosome are small molecules selectively released from breast cancer cells to the peripheral circulation for a certain period of time. miRNA contained in them are short, non-coding regulatory RNA, which can bind to the 3′UTR region of target genes and regulate the post-transcriptional expression of target genes. Exogenous miRNA can affect the development of breast cancer, It can provide a variety of information indicating the presence of breast cancer cells, clinical staging, molecular typing and other information, which may be put into clinical application in the future as an ideal marker for the early diagnosis of breast cancer.This article reviews the research and application of exogenous miRNA in early diagnosis of breast cancer.

Objective To evaluate the stability of U6 and let-7a as internal reference genes of miRNAs in RTqPCR by using femoral head samples of cartilage tissue from inbred DA rats.Methods Total RNA was extracted from femoral head cartilage tissues of female DA rats at three different time points,i.e.at birth (D0),ablactation (D21) and maturation (D42).The expressions of different miRNAs (miR-1,-25,-26a,-140,-146a,-150,-181a,-195,-223 and-337) were detected by RT-qPCR using U6 or let-7a as the internal reference.The two sets of miR expression were compared with the results from Solexa sequencing in our pioneer work to evaluate the stability of the two internal references.Results The relative values of U6 (P =0.045) and let-7a (P =0.021 5) revealed significant difference in the D42 sample.Both in U6 and let-7a systems,miR-26a,-140,-223,and-337 showed a similar tendency in expression and quantification but miR-1 and-146a did not have significant differences.miR-25,-150,-181a and-195 differed significantly (P＜0.05).Comparison of absolute quantification results between the two generations' sequencing showed that let-7a is more stable than U6.Conclusion Let-7a is more suitable to be used as the internal reference gene in RT-qPCR for miRNAs in cartilage tissue.

Purpose To analyze the correlations between PD-L1 expression and clinicopathological factors and their prognostic values in esophageal squamous cell carcinoma (ESCC) patients.Methods PD-L1 expression in the primary tumors from 253 patients with ESCC was evaluated using tissue microarray and immunohistochemistry (IHC).PD-L1 positivity was defined as positive staining of 1％ and 5％ tumor cells.Survival curves were constructed by using the Kaplan-Meier method.Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results Overall,tumoral PD-L1 expression was potentially associated with favorable DFS and OS.When the patients were stratified into stage Ⅰ + Ⅱ (60.9％,154/253) and stage Ⅲ + Ⅳa (39.1％,99/253),the prognostic role was not consistent.In patients with stage Ⅰ + Ⅱ disease,tumoral PD-L1 expression was associated with better DFS and OS upon multivariate analysis (1％ as the cutoff:P =0.046 and 0.021,5％ as the cutoff:P=0.011 and0.004).However,PD-L1 expression was not correlated with prognosis in patients with stage Ⅲ + Ⅳa disease (1％ as the cutoff:P =0.586 and 0.682,5％ as the cutoff:P =0.807 and 0.620).Conclusion The prognostic role of tumoral PDL expression is variable in different stages of ESCC,and tumoral PDL expression is an independent favorable predictor in ESCC patients with Stage Ⅰ-Ⅱ disease,but not in stage Ⅲ-Ⅳa or lymph node metastasis.