The development of breast cancer is closely related to the information transfer in its microenvironment.As a novel information communication tool,exosomes present non-coding RNAs that are involved in breast cancer cell proliferation,migration,invasion,tumour-associated fibroblasts ogenesis,cell cycle,degradation of oncogenes,etc.This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.

OBJECTIVE: To explore clinical efficacy of percutaneous endoscopic discectomy with a lateral approach and dual-channel method in treating highly free lumbar disc herniation(LDH). METHODS: A retrospective analysis was conducted on 54 patients with highly free LDH who were treated with spinal endoscopic techniques from January 2021 to December 2022. Twenty-seven patients were treated with lateral approach dual-channel(lateral approach dual-channel group), including 16 males and 11 females, with an average age of (54.6±10.5) years old. Twenty-seven patients were treated with unilateral biportal endoscopic (UBE group), including 17 males and 10 females, with an average age of (52.9±12.3) years old. The number of intraoperative fluoroscopy, operation time and hospital stay, as well as visual analogue scale (VAS) and Oswestry diability index (ODI) of low back and leg pain between two patients before operation, 1 day, 1, 3, and 12 months after operation, and the efficacy was evaluated by the modified MacNab criteria at 12 mohths after operation. RESULTS: All patients were successfully completed surgical and were followed up, the time raged from 12 to 22 months with an average of (13.57±4.12) months. There was no statistically significant difference in operation time between two groups (P>0.05). The hospital stay of lateral approach dual-channel group was (3.9±1.1) days, which was shorter than that of UBE group (6.5±1.4) days, the number of intraoperative fluoroscopy in lateral approach dual-channel group was (12.7±2.1) times, which was more than that in UBE group (6.6±1.3) times, the differences were statistically significant (t=5.197, -7.532;P<0.05). VAS and ODI for low back pain at 1 day and 1 month after operation, and VAS for leg pain at 1 day after operation of lateral approach dual-channel group were superior to those of UBE group, and the differences were statistically significant (P<0.05). However, there were no statistically significant differences in VAS and ODI for low back and leg pain between two groups before operation and 3 and 12 months after operation (P>0.05). VAS and ODI of low back and leg pain were significantly improved at each time point before and after operation in both groups, and the difference were statistically significant (P<0.05). At 12 months after operation, according to the modified MacNab criteria, the excellent and good rates of therapeutic effects between lateral approach dual-channel group and UBE group were 92.6% (25/27) and 88.9% (24/27), respectively, and the difference was not statistically significant (χ²=0.22, P>0.05). CONCLUSION For patients with highly free lumbar intervertebral disc protrusion, both of lateral approach dual-channel method and UBE endoscopic surgery are safe and effective. Endoscopic surgery with lateral approach and dual-channel method could be performed under local anesthesia, allowing for the removal of the nucleus pulposus under direct vision. It is simpler, more efficient.
Humans ; Male ; Female ; Intervertebral Disc Displacement/surgery* ; Middle Aged ; Diskectomy, Percutaneous/methods* ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Adult ; Retrospective Studies ; Aged

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

The development of breast cancer is closely related to the information transfer in its microenvironment.As a novel information communication tool,exosomes present non-coding RNAs that are involved in breast cancer cell proliferation,migration,invasion,tumour-associated fibroblasts ogenesis,cell cycle,degradation of oncogenes,etc.This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective:To evaluate the efficacy, adverse reactions and compliance of vonoprazan (VPZ) dual therapy and bismuth-containing quadruple therapy with low-resistance antibiotics in the initial treatment of primary Helicobacter pylori ( H. pylori) infection. Methods:From March 7, 2022 to August 25, 2023, a total of 200 patients with H. pylori infection who visited the Department of Gastroenterology and Hepatology of the University of Hong Kong-Shenzhen Hospital were selected. According to the random number table method, the patients were randomly divided into the VPZ combined with amoxicillin treatment group (hereinafter referred as VPZ dual therapy group) and the proton pump inhibitor (PPI), tetracycline, full-dose (1 600 mg/d) metronidazole and bismuth treatment group (hereinafter referred as PPI quadruple therapy group). The patients of VPZ dual therapy group were given VPZ 20 mg (twice a day) combined with amoxicillin 1 000 mg (3 times a day), and the patients of PPI quadruple therapy group were given esomeprazol 20 mg (2 times a day), bismuth 0.6 g (twice a day), metronidazole 400 mg (4 times a day), and tetracycline 500 mg (3 times a day). The patients of both groups were treated for 14 days. The H. pylori infection status was re-examined 4 weeks after drug withdrawal. The results were analyzed by intention-to-treat (ITT) analysis, modified ITT analysis and per-protocol analysis (PPA). One-sided μ test was used for non-inferiority evaluation, and two-sided 95% confidence interval (95% CI) was obtained. Chi-square test was used for statistical analysis. Results:In the ITT analysis, 92.0% (92/100) of patients in the VPZ dual therapy group and 77.0% (77/100) of patients in the PPI quadruple therapy group completed the 14-day treatment, and the difference was statistically significant ( χ2=8.59, P=0.003). In the ITT analysis, the H. pylori eradication rates in the VPZ dual therapy group and the PPI quadruple therapy group were 96.0% (96/100) and 92.0% (92/100), respectively, and the difference was statistically significant (difference=4.0%, 95% CI -2.9% to 11.5%, P<0.001). In the modified ITT analysis, the H. pylori eradication rates of the VPZ dual therapy group and the PPI quadruple therapy group were 97.0% (96/99) and 95.8% (92/96), respectively, and the difference was statistically significant (difference=1.1%, 95% CI -4.9% to 7.6%, P=0.002). In the PPA, the H. pylori eradication rates of the VPZ dual therapy group and the PPI quadruple therapy group were 96.7% (89/92) and 97.4% (75/77), respectively, and the difference was statistically significant (difference=-0.7%, 95% CI -6.9% to 6.1%, P=0.009). In the ITT analysis, the incidence of adverse reaction in the VPZ dual therapy group was lower than that in the PPI quadruple therapy group (39.0%, 39/100 vs. 71.0%, 71/100), and the difference was statistically significant ( χ2=20.69, P<0.001). Conclusion:In initial treatment of H. pylori infection, the eradication rate of VPZ dual therapy is non-inferior to that of PPI quadruple therapy, and VPZ dual therapy demonstrates higher safety.

Objective:To evaluate the efficacy, adverse reactions and compliance of vonoprazan (VPZ) dual therapy and bismuth-containing quadruple therapy with low-resistance antibiotics in the initial treatment of primary Helicobacter pylori ( H. pylori) infection. Methods:From March 7, 2022 to August 25, 2023, a total of 200 patients with H. pylori infection who visited the Department of Gastroenterology and Hepatology of the University of Hong Kong-Shenzhen Hospital were selected. According to the random number table method, the patients were randomly divided into the VPZ combined with amoxicillin treatment group (hereinafter referred as VPZ dual therapy group) and the proton pump inhibitor (PPI), tetracycline, full-dose (1 600 mg/d) metronidazole and bismuth treatment group (hereinafter referred as PPI quadruple therapy group). The patients of VPZ dual therapy group were given VPZ 20 mg (twice a day) combined with amoxicillin 1 000 mg (3 times a day), and the patients of PPI quadruple therapy group were given esomeprazol 20 mg (2 times a day), bismuth 0.6 g (twice a day), metronidazole 400 mg (4 times a day), and tetracycline 500 mg (3 times a day). The patients of both groups were treated for 14 days. The H. pylori infection status was re-examined 4 weeks after drug withdrawal. The results were analyzed by intention-to-treat (ITT) analysis, modified ITT analysis and per-protocol analysis (PPA). One-sided μ test was used for non-inferiority evaluation, and two-sided 95% confidence interval (95% CI) was obtained. Chi-square test was used for statistical analysis. Results:In the ITT analysis, 92.0% (92/100) of patients in the VPZ dual therapy group and 77.0% (77/100) of patients in the PPI quadruple therapy group completed the 14-day treatment, and the difference was statistically significant ( χ2=8.59, P=0.003). In the ITT analysis, the H. pylori eradication rates in the VPZ dual therapy group and the PPI quadruple therapy group were 96.0% (96/100) and 92.0% (92/100), respectively, and the difference was statistically significant (difference=4.0%, 95% CI -2.9% to 11.5%, P<0.001). In the modified ITT analysis, the H. pylori eradication rates of the VPZ dual therapy group and the PPI quadruple therapy group were 97.0% (96/99) and 95.8% (92/96), respectively, and the difference was statistically significant (difference=1.1%, 95% CI -4.9% to 7.6%, P=0.002). In the PPA, the H. pylori eradication rates of the VPZ dual therapy group and the PPI quadruple therapy group were 96.7% (89/92) and 97.4% (75/77), respectively, and the difference was statistically significant (difference=-0.7%, 95% CI -6.9% to 6.1%, P=0.009). In the ITT analysis, the incidence of adverse reaction in the VPZ dual therapy group was lower than that in the PPI quadruple therapy group (39.0%, 39/100 vs. 71.0%, 71/100), and the difference was statistically significant ( χ2=20.69, P<0.001). Conclusion:In initial treatment of H. pylori infection, the eradication rate of VPZ dual therapy is non-inferior to that of PPI quadruple therapy, and VPZ dual therapy demonstrates higher safety.