OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

Objective:To investigate the expression and clinical significance of zinc finger protein Kruppel-like factor 4 (KLF4) and topoisomeraseⅡalpha (TOP2A) in breast cancer.Methods:From Jan. 2022 to Jun. 2023, 126 patients with breast cancer were selected for examination in the clinical Laboratory of the First Affiliated Hospital of Inner Mongolia Medical University. Breast cancer tissues and adjacent tissues of all patients were collected. The expressions of KLF4 and TOP2A were detected by immunohistochemical staining, and the relationship of the expressions of KLF4 and TOP2A with the pathological features of patients was analyzed. Patients were divided into recurrence group and non-recurrence group according to whether they had recurrence after surgery. The expression of KLF4 and TOP2A in the two groups were compared. Spearman correlation analysis was used to analyze the relationship of KLF4 and TOP2A with breast cancer recurrence, and multivariate Cox risk regression was used to analyze the risk factors of breast cancer recurrence after surgery.Results:The positive expression rate of KLF4 in tumor tissues was lower than that in paracancer tissues, and the positive expression rate of TOP2A was higher ( χ 2=35.24, 53.89, P<0.001) ; The levels of KLF4 and TOP2A in tumor tissues were correlated with TNM stage, differentiation degree, borderline state and lymph node metastasis ( χ 2=10.98, 8.49, 4.28, 7.28, P=0.001, 0.004, 0.039, 0.007; χ 2=8.15, 8.78, 6.39, 7.20, P=0.004, 0.003, 0.011, 0.007), and the expression of TOP2A was correlated with the pathological type ( χ 2=4.31, P=0.04) ; The recurrence rate in KLF4 negative expression group and TOP2A positive expression group was higher than that in KLF4 positive expression group and TOP2A negative expression group ( χ 2=4.53, 5.92, P=0.033, 0.015) ; Spearman correlation analysis showed that positive expression of KLF4 was negatively correlated with breast cancer recurrence ( r=-0.43, P<0.001), and positive expression of TOP2A was positively correlated with breast cancer recurrence ( r=0.51, P<0.001) ; Multivariate Cox regression analysis showed that TNM stage, lymph node metastasis, negative KLF4 expression and positive TOP2A expression were independent risk factors for breast cancer recurrence ( P<0.05) . Conclusion:KLF4 is negatively expressed in breast cancer tissues, while TOP2A is positively expressed, and its expression level is closely related to pathological characteristics and has certain evaluation value for postoperative recurrence of breast cancer.

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Objective:Based on the functional classification structure of the International Classification of Functioning, Disability and Health′s rehabilitation set (ICF-RS), the data available in the open database of the China Health and Retirement Longitudinal Study (CHARLS) were analyzed longitudinally to construct the development trajectories of different functional dimensions among China′s elderly population.Methods:The CHARLS data for 2013, 2015 and 2018 describing persons aged 60 and older were distributed using the ICF-RS′s classification structure. Group-based multi-trajectory modeling (GBMTM) was then applied to analyze the characteristics of the development trajectories of physical functioning, daily activities and social participation.Results:Different development trajectory subtypes emerged from the data. A gradual decline in physical functioning was evident throughout the study period, while daily activities first improved and then declined. Social participation was in decline throughout the period. There were, however, significant differences in the initial functional level, the degree of decline and the degree of decline reversal among the different subtype groups.Conclusions:The overall functional performance of the elderly in China shows a downward trend, but some functional dimensions can still improve with time, at least during the specific period covered in this open database. It is recommended that the ICF-RS be integrated into the CHARLS to comprehensively assess the classification of function and developmental changes among China′s elderly.

Objective To explore the efficacy of a model combining clinicopathological characteristics and multiparametric MRI features for predicting BRCA-mutated breast cancer(BC).Methods A total of 256 BC patients were retrospectively selected and divided into BRCA mutation group(116 cases)and BRCA wild group(140 cases)based on the BRCA results.Chi-square tests or independ-ent sample t-tests were used to compare the differences in clinicopathological characteristics and multiparametric MRI features between the BRCA mutation group and the wild group.Risk factors for BRCA-mutated BC were identified through univariate and multivariate logistic regression ananlyses,and a combined predictive model was constructed.Receiver operating characteristic(ROC)curve was used to ana-lyze the diagnostic efficacy of the model.Results There were statistically significant differences in T stage,human epidermal growth factor receptor 2(HER-2),Ki-67,non-mass enhancement,enhancement pattern,time-signal intensity curve(TIC)type,and apparent diffusion coefficient(ADC)values between the BRCA mutation group and the wild group.Univariate logistic regression analysis showed that T stage,HER-2,Ki-67,non-mass enhancement,enhancement pattern,TIC type,and ADC values were risk factors for BRCA-mutated BC(P<0.05).Multivariate logistic regression analysis revealed that T stage,HER-2,Ki-67,enhancement pattern,and TIC type were independent risk factors for BRCA-mutated BC(P<0.05).The combined model incorporating T stage,HER-2,Ki-67,enhancement pattern,and TIC type had the best diagnostic efficacy in predicting BRCA-mutated BC,with an area under the curve(AUC)of 0.751.Conclusion The combined model integrating T stage,HER-2,Ki-67,enhancement pattern,and TIC type has good efficacy in predicting BRCA-mutated BC.

Objective:To investigate the expression and clinical significance of zinc finger protein Kruppel-like factor 4 (KLF4) and topoisomeraseⅡalpha (TOP2A) in breast cancer.Methods:From Jan. 2022 to Jun. 2023, 126 patients with breast cancer were selected for examination in the clinical Laboratory of the First Affiliated Hospital of Inner Mongolia Medical University. Breast cancer tissues and adjacent tissues of all patients were collected. The expressions of KLF4 and TOP2A were detected by immunohistochemical staining, and the relationship of the expressions of KLF4 and TOP2A with the pathological features of patients was analyzed. Patients were divided into recurrence group and non-recurrence group according to whether they had recurrence after surgery. The expression of KLF4 and TOP2A in the two groups were compared. Spearman correlation analysis was used to analyze the relationship of KLF4 and TOP2A with breast cancer recurrence, and multivariate Cox risk regression was used to analyze the risk factors of breast cancer recurrence after surgery.Results:The positive expression rate of KLF4 in tumor tissues was lower than that in paracancer tissues, and the positive expression rate of TOP2A was higher ( χ 2=35.24, 53.89, P<0.001) ; The levels of KLF4 and TOP2A in tumor tissues were correlated with TNM stage, differentiation degree, borderline state and lymph node metastasis ( χ 2=10.98, 8.49, 4.28, 7.28, P=0.001, 0.004, 0.039, 0.007; χ 2=8.15, 8.78, 6.39, 7.20, P=0.004, 0.003, 0.011, 0.007), and the expression of TOP2A was correlated with the pathological type ( χ 2=4.31, P=0.04) ; The recurrence rate in KLF4 negative expression group and TOP2A positive expression group was higher than that in KLF4 positive expression group and TOP2A negative expression group ( χ 2=4.53, 5.92, P=0.033, 0.015) ; Spearman correlation analysis showed that positive expression of KLF4 was negatively correlated with breast cancer recurrence ( r=-0.43, P<0.001), and positive expression of TOP2A was positively correlated with breast cancer recurrence ( r=0.51, P<0.001) ; Multivariate Cox regression analysis showed that TNM stage, lymph node metastasis, negative KLF4 expression and positive TOP2A expression were independent risk factors for breast cancer recurrence ( P<0.05) . Conclusion:KLF4 is negatively expressed in breast cancer tissues, while TOP2A is positively expressed, and its expression level is closely related to pathological characteristics and has certain evaluation value for postoperative recurrence of breast cancer.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective:To investigate the clinical effect of the transfer of lateral femoral fascia or combined with anteriolateral thigh flap (ALTF) on treatment of defects of Achilles tendon and surrounding soft tissue.Methods:From May 2004 to December 2021, 15 patients with Achilles tendons defects were treated with the transfer of either lateral femoral fascia or combined with ALTF in the Department of Hand and Foot Microsurgery, Xi'an Fengcheng Hospital. Two of the patients had postoperative infection after the primary treatment for Achilles tendon rupture and 13 patients had Achilles tendon defect together with various grade of defects of surrounding soft tissues. According to the size of wound, ALTFs and lateral superior knee flaps were used for the reconstructions. Various complex tissue flaps were used in reconstructive surgery: ALTF in 10 patients, the lateral thigh muscular flap in 3 patients and the lateral knee artery flap in 5 patients. The length of Achilles tendon defect was 3.0-8.0 cm and the length of fascia was 4.0-9.0 cm. The sizes of the flaps were 4.0 cm×3.0 cm-30.0 cm×18.0 cm. After the fascia and the flaps were harvested, the fascia was rolled up or wrapped up around the muscle with the knee at 30° flexion and the ankle at 30° flexion. Then end-to-end or end-to-side blood vessel anastomoses were carried out. The ALTFs were used to cover the wounds.Results:All the 15 flaps survived. After 2 to 5 years of follow-up, the heel lift test was found negative, without re-broken of Achilles tendon. All patients were in normal walking gait, except 2 patients who had mild lameness. According to the Amer-Lindholm scoring criteria, the results were excellent in 13 patients and good in 2 patients.Conclusion:Lateral thigh composite tissue transfer is an effective method to reconstruct Achilles tendon and the defects of its surrounding tissues.

Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.

Objective To explore the efficacy of a model combining clinicopathological characteristics and multiparametric MRI features for predicting BRCA-mutated breast cancer(BC).Methods A total of 256 BC patients were retrospectively selected and divided into BRCA mutation group(116 cases)and BRCA wild group(140 cases)based on the BRCA results.Chi-square tests or independ-ent sample t-tests were used to compare the differences in clinicopathological characteristics and multiparametric MRI features between the BRCA mutation group and the wild group.Risk factors for BRCA-mutated BC were identified through univariate and multivariate logistic regression ananlyses,and a combined predictive model was constructed.Receiver operating characteristic(ROC)curve was used to ana-lyze the diagnostic efficacy of the model.Results There were statistically significant differences in T stage,human epidermal growth factor receptor 2(HER-2),Ki-67,non-mass enhancement,enhancement pattern,time-signal intensity curve(TIC)type,and apparent diffusion coefficient(ADC)values between the BRCA mutation group and the wild group.Univariate logistic regression analysis showed that T stage,HER-2,Ki-67,non-mass enhancement,enhancement pattern,TIC type,and ADC values were risk factors for BRCA-mutated BC(P<0.05).Multivariate logistic regression analysis revealed that T stage,HER-2,Ki-67,enhancement pattern,and TIC type were independent risk factors for BRCA-mutated BC(P<0.05).The combined model incorporating T stage,HER-2,Ki-67,enhancement pattern,and TIC type had the best diagnostic efficacy in predicting BRCA-mutated BC,with an area under the curve(AUC)of 0.751.Conclusion The combined model integrating T stage,HER-2,Ki-67,enhancement pattern,and TIC type has good efficacy in predicting BRCA-mutated BC.