BACKGROUND:There are some problems such as bone fusion failure or peri-implant infection after implantation of pure titanium implants.Therefore,surface improvement of titanium implants has become a hot topic in research.Macrophages are an immune defense line of the body in response to external stimuli,and the relevant immune response of any biomaterials implanted in the body is related to macrophages. OBJECTIVE:The graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The surface characteristics of the coating and the growth and polarization of macrophage RAW264.7 on the surface were analyzed. METHODS:The graphene oxide coating and graphene oxide/hydroxyapatite composite coating on titanium alloy surface was prepared by electrochemical deposition method.The physical properties of the coating were characterized.Pure titanium sheets(blank group),titanium sheets deposited with pure GO coating(control group)and titanium sheets deposited with graphene oxide/hydroxyapatite composite coating(experimental group)were co-cultured with macrophages RAW264.7,respectively.Cell proliferation was detected by CCK-8 assay and DAPI staining.Cell adhesion on the surface of titanium was observed by scanning electron microscopy,and cell polarization phenotype was detected by flow cytometry. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the pure titanium sheet showed directional scratches and a few punctate pits.After the pure graphene oxide coating was deposited,the surface of titanium sheet showed more cracks,gullies and particles of uneven size,and the wrinkle-like structure characterized by graphene oxide.After the composite coating was deposited,the surface of the titanium sheet was smooth,and the pellet size was more uniform.The water contact angle of composite coated titanium sheet was lower than that of pure titanium sheet and pure graphene oxide coated titanium sheet(P<0.05).(2)CCK-8 assay and DAPI staining showed that compared with the blank group and the control group,the cell proliferation in the experimental group was faster.Scanning electron microscopy showed that RAW264.7 cells all adhered to the surface of the three groups of titanium sheets.With the extension of culture time,cell morphology changed from round to spindle shape.After 7 days of culture,cells in the blank group extended short and few pseudopods;cells in the control group extended long and more pseudopods,and cells in the experimental group extended short and more pseudopods,and the overall cell fullness in the experimental group was the best.Flow cytometry results showed that the cells in the experimental group showed a higher proportion of M2 polarization in the anti-inflammatory direction.(3)These findings conclude that graphene oxide/hydroxyapatite composite coating has good physical,chemical,and biological properties.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective To explore the therapeutic effects of temperature-controlled radiofrequency combined with electrical stimulation biofeedback on postpartum dyspareunia in women.Methods In this study,166 patients suffering from dyspareunia due to pelvic floor muscle hypertonicity who visited the Pelvic Floor Rehabilitation Medicine Center of our hospital were selected as subjects.They were randomly divided into three groups:the electrical stimulation biofeedback treatment group(55 cases),the radiofrequency treatment group(55 cases),and the combined electrical stimulation biofeedback and radiofrequency treatment group(56 cases).Patients in the electrical stimulation biofeedback therapy group received only electrical stimulation biofeedback therapy;patients in the radiofrequency group were treated solely with radiofrequency therapy;and patients in the combined treatment group began receiving gynecological radiofrequency treatment from the second week,in addition to the same treatment as the electrical stimulation biofeedback treatment group.To evaluate the effectiveness of the three treatment methods,comparative analyses were conducted on the pelvic floor modified Oxford muscle strength measurement results,pelvic floor surface electromyography values,and sexual function(FSFI)scores of the three groups of patients before and after treatment.Results After treatment,the average resting electromyography(EMG)value of the combined treatment group decreased(P＜0.05),indicating a significant improvement in muscle relaxation function.After treatment,the combined treatment group showed significant improvements in the pelvic floor modified Oxford muscle strength test,the maximum EMG value of fast-twitch(type Ⅱ fibers)muscles,the average EMG value of slow-twitch(type Ⅰ fibers)muscles,and the average EMG value of endurance test,and also demon-strated significant improvements in sexual function(FSFI)scores,which were superior to the electrical stimulation biofeedback treatment group and the radiofrequency treatment group(P＜0.05).Conclusion The combined treatment of temperature control radiofrequency and electrical stimulation with biofeedback has shown significant therapeutic effects in the treatment of postpartum dyspareunia,offering a broad prospect for clinical application.

Objective To investigate the clinical efficacy of intravaginal CO2 fractional laser combined with interferon in treating persistent high-risk HPV infection of the cervix and its impact on vaginal microecology.Methods A total of 211 patients with persistent high-risk HPV infection of the cervix who visited Kunming Maternal and Child Health Care Hospital from June 2022 to July 2024 were selected and randomly divided into a follow-up(blank control)group(n=70),an interferon treatment group(n=70),and a combined treatment group(n=71).The follow-up group received regular follow-ups.The interferon treatment group was treated with recombinant human interferon α-2b,and the combined treatment group received a combination of CO2 matrix laser and interferon treatment.The total effective rate,levels of inflammatory factors,and vaginal microecological recovery were compared among the three groups at 3 and 6 months after treatment.Results Overall efficacy:The overall efficacy rates of the combined treatment group at 3 months and 6 months were 73.24%and 81.69%,respectively,significantly higher than those of the interferon group(47.14%and 60.00%)and the blank control group(11.43%and 18.57%)(all P<0.001).Inflammatory factors:Post-treatment levels of IL-1 and TNF-α in the combined treatment group were significantly lower than those in the other two groups(P<0.001).Vaginal microbiota:The combined treatment group had a significantly higher rate of normal PH(84.51%)and normal lactobacillus levels(92.96%)compared to the other two groups(P<0.001).Conclusion CO2 lattice laser combined with interferon can effectively eliminate HPV,improve inflammation and vaginal microenvironment,and demonstrates superior efficacy to monotherapy,with good safety.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

The precise assessment and management of the axillary lymph nodes in breast cancer is crucial for regional control, disease staging, selection of adjuvant chemotherapy strategies, and prediction of prognosis, with a general downward trend in surgical management. For early breast cancer with negative axillary lymph node metastases, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the criterion for axillary status measurement. Patients can be exempted from ALND if they have negative SLNB results. However, it remains to be carefully decided in China whether patients with one or two positive nodes in SLNB can be spared from ALND. However, consensus has been met that patients who meet the criteria of the Z0011 study can be exempted from ALND. For breast cancer patients with positive axillary lymph nodes metastases at the beginning of treatment, the clearance of lymph node disease can be achieved by neoadjuvant therapy, with a reduced rate of complications related to ALND. In particular, there are still many debates associated with SLNB after neoadjuvant therapy, such as whether patients who remain axillary lymph node positive can be spared from ALND. Exploratory and validation studies related to the SLNB avoidance criteria are still controversial. In the future, clinicians should consider the characteristics of patients, the risk of recurrence, and adjuvant treatment regimens to develop individualized axillary lymph node management.

The precise assessment and management of the axillary lymph nodes in breast cancer is crucial for regional control, disease staging, selection of adjuvant chemotherapy strategies, and prediction of prognosis, with a general downward trend in surgical management. For early breast cancer with negative axillary lymph node metastases, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the criterion for axillary status measurement. Patients can be exempted from ALND if they have negative SLNB results. However, it remains to be carefully decided in China whether patients with one or two positive nodes in SLNB can be spared from ALND. However, consensus has been met that patients who meet the criteria of the Z0011 study can be exempted from ALND. For breast cancer patients with positive axillary lymph nodes metastases at the beginning of treatment, the clearance of lymph node disease can be achieved by neoadjuvant therapy, with a reduced rate of complications related to ALND. In particular, there are still many debates associated with SLNB after neoadjuvant therapy, such as whether patients who remain axillary lymph node positive can be spared from ALND. Exploratory and validation studies related to the SLNB avoidance criteria are still controversial. In the future, clinicians should consider the characteristics of patients, the risk of recurrence, and adjuvant treatment regimens to develop individualized axillary lymph node management.

Objective:To explore the application value of non-invasive myocardial work imaging in evaluating the cardiac function of ST-segment elevation myocardial infarction (STEMI) patients with left ventricular remodeling (LVR) after percutaneous coronary intervention (PCI).Methods:One hundred and twenty-six patients with STEMI undergoing PCI in General Hospital of Ningxia Medical University from December 2021 to September 2022 were prospectively collected and divided into left ventricular remodeling group (LVR group, 34 cases) and non left ventricular remodeling group (NLVR group, 92 cases) according to whether there was left ventricular remodeling 3 months after surgery. General data were collected. Routine echocardiography and noninvasive myocardial work imaging were performed before, 1 week, 1 month, and 3 months after surgery, the differences in the above parameters between the two groups were compared. Pearson correlation analysis was used to analyze the correlation between the indicators.Logistic regression analysis was used to determine the independent risk factors of left ventricular remodeling after STEMI, and a predictive model was obtained. The diagnostic value of the model was judged by ROC curve.Results:①General information comparison: There were statistically significant differences between the two groups in BMI, systolic blood pressure, diastolic blood pressure, average number of stents implanted, and history of hyperlipidemia (all P<0.05), but there was no significant difference in other data (all P>0.05). There was no statistically significant difference in two-dimensional transthoracic echocardiography (2D-TTE) parameters and non-invasive myocardial work (MW) parameters between the two groups before and 1 week after operation (both P>0.05). ②2D-TTE parameter comparison: LVESV and LVEDV at 3 months after PCI in the LVR group were significantly higher than those in the NLVR group, and LVEF and E/A were significantly lower than those in the NLVR group (all P<0.05); There were no significant differences in other indexes between the two groups by conventional echocardiography at 3 months after PCI(all P>0.05). ③Comparisons of noninvasive myocardial work parameters: GLS, GWE, GWI, GCW at 1 month and 3 months after PCI in the LVR group were significantly lower than those in the NLVR group, and GWW were significantly higher than those in the NLVR group ( P<0.001). ④Correlation analysis: GLS, GWE, GCW, GWI and LVEDV were negatively correlated at 1 month after operation ( r=-0.42, -0.38, -0.50, -0.53, all P<0.001), GWW was positively correlated with LVEDV ( r=0.45, P<0.001). ⑤Logistic regression analysis: GLS<17%, GCW<1 900 mmHg%, GWW>105 mmHg%, and GWE<90 mmHg% at 1 month after PCI were independent predictors for LVR in STEMI patients after PCI (all P<0.05). The predictive model was Logit (P)=0.692GLS+ 0.804GCW+ 0.972GWW+ 0.880GWE. The AUC of this model was 0.886, 95% CI=0.845-0.926, which was significantly higher than single index, the sensitivity was 0.86, and the specificity was 0.79. Conclusions:GLS, GWE, GWI, GCW are positively correlated with LVR, while GWW is negatively correlated with left ventricular remodeling. Noninvasive myocardial work parameters are independent risk factors for left ventricular remodeling in patients with STEMI after PCI surgery. This technique can be used to evaluate LVR and has great clinical application value.

Objective:To explore the value of ultrasound-based radiomics combined with clinical parameters in predicting lymph node metastasis of endometrial cancer.Methods:The clinical data and preoperative ultrasound images of 255 patients with endometrial cancer diagnosed after operation in the First Affiliated Hospital of Guangxi Medical University from January 2017 to February 2021 were analyzed retrospectively. The boundary of the tumor, that is, the region of interest(ROI), was determined manually by ITK-SNAP software, and the features were extracted from it. Through random sampling, the data were divided into training group used to build the model and verification group used to evaluate the reliability of the model at the proportion of 7∶3.In the training group, the spearman correlation coefficient was used as the threshold of 0.95 to remove the features with high correlation. The importance of the features were ranked by the decision tree model, the features of the top 6% importance were selected to establish a logical regression model, and then calculated the Radiomics score of each patient. On the basis of logical regression analysis, a comprehensive prediction model was established, the line diagram was drawn, and the prediction effect was evaluated by the analysis of the area under the subject working curve (AUC), calibration curve and the decision curve.Results:After dimensionality reduction and logical regression analysis, 20 features and 2 clinical parameters (CA125, CA153) were obtained to build the model. The AUC of training group and verification group in radiomics model and comprehensive prediction model were 0.81, 0.78 and 0.89, 0.85, respectively. The decision curve analysis showed that both of them had good clinical utility.Conclusions:The ultrasound-based radiomics model and the comprehensive model combined with relevant clinical parameters are effective in predicting lymph node metastasis of endometrial cancer.