Pattern recognition receptors (PRRs) play a crucial role in immune responses, acting as primary sensors for microbial and host-derived signals. PRRs, which include Toll-like receptors (TLRs), retinoic acid-inducible gene 1-like receptors, nucleotide-binding oligomerization domain-like receptors, C-type lectin receptors, and various cytoplasmic DNA sensors, are essential for initiating immune responses that regulate both inflammation and tumor immunity. Recent studies have highlighted their dual roles in cancer, where they can either suppress or promote tumor progression by influencing the tumor microenvironment and modulating responses to immunotherapy. In the context of cancer, PRRs not only activate immune cells but also contribute to immune evasion mechanisms within tumors. Therapeutically, targeting PRRs represents a promising approach for cancer treatment, with related drugs showing potential to enhance the efficacy of existing immunotherapies. Numerous PRR-based agents, particularly TLR agonists, are currently under clinical investigation for their ability to augment antitumor immunity and overcome resistance to immune checkpoint inhibitors. This review examines the molecular mechanisms by which PRRs influence cancer, with a focus on recent advancements in PRR-targeted therapies and their integration with contemporary immunotherapeutic strategies.

Objective:To evaluate cerebrospinal fluid (CSF) flow dynamics and volume changes of pulsatile tinnitus (PT) patients induced by sigmoid sinus wall dehiscence (SSWD) using MRI.Methods:This was a cross-sectional study. Totally 55 SSWD-PT patients, and 35 age- and sex-matched healthy controls were prospectively enrolled at Beijing Tongren Hospital, Capital Medical University from October 2019 to September 2023. The CSF at the midbrain aqueduct level was analyzed based on phase-contrast MRI to obtain the flow dynamics information. Based on T 1-weighted turbo field echo sequence, the CSF was segmented and the volume of CSF was calculated using ITK-SNAP software. The Mann-Whitney U test was used to compare the differences of each parameter between the two groups. Binary logistic regression was used to analyze the parameters with statistically significant differences to obtain the independent influencing factors of SSWD-PT and establish the combined parameters. Receiver operating characteristic curve analysis was used to evaluate the efficacy of diagnosing SSWD-PT. Results:Compared with controls, the SSWD-PT group showed significantly decreased mean flux (MF), mean velocity, peak velocity( P<0.05), and significantly increased regurgitant fraction (RF), CSF volume ( P<0.05). No significant differences were observed in forward flow volume, backward flow volume, and stroke volume ( P>0.05). The logistic regression results showed that MF ( OR=0.497, 95% CI 0.305-0.808, P=0.005) and RF ( OR=1.809, 95% CI 1.040-3.147, P=0.036) were independent influencing factors of SSWD-PT. The area under the curve (AUC) of MF and RF for diagnosing SSWD-PT were 0.641 (95% CI 0.517-0.766) and 0.675 (95% CI 0.564-0.786), respectively. The AUC of the combination of MF and RF was 0.724 (95% CI 0.614-0.833). Conclusions:SSWD-PT patients have abnormal changes in CSF flow dynamics and volume. The MF and RF demonstrate moderate diagnostic value for diagnosing SSWD-PT.

Objective: To explore the relationship between related factors of non-suicidal self-injury behavior (NSSI) among middle school students in Guizhou Province, so as to provide the evidence for preventing high risk behaviors in adolescents. Methods: A stratified cluster random sampling method was used to select 1 034 junior and senior middle school students from Zunyi City, Qiannan Prefecture and Tongren City in Guizhou Province from April to October in 2023. Questionnaire survey was conducted to collect information including Adolescent Self injury Scale and Family Assessment Device. The R 4.4.1 software was employed for network analysis visualization, centrality indicators, and result stability assessment. Results: The detection rate of NSSI behavior among middle school students in Guizhou province was 29.6%, with a detection rate of 25.5% for boys and 33.1% for girls, showing a statistically significant difference ( χ 2=7.07, P <0.05). There were statistically significant differences in scores of emotional communication, egoism, family rules, positive communication, problem solving, expression of positive emotions and management of negative emotions self-efficacy, and bullying victimization in various dimensions between middle school students with and without NSSI ( Z =-13.66 to -7.05, P <0.01). NSSI among middle school students was positively correlated with social/relational bullying, depression and anxiety, and there were relatively close connections in the network ( r =0.35, 0.43, 0.42, P <0.01). Centrality indicators showed that the highest in strength and closeness centrality were stress ( Z =1.29, 1.58), the highest in betweenness centrality was for emotional communication ( Z =1.91), and the highest in expected influence index was for physical bullying ( Z =1.44)( P < 0.05). Conclusions Stress, emotional communication and physical bullying have significant impacts in the network of factors related to NSSI. Social/relational bullying, depression and anxiety have strong direct correlations with NSSI behavior among middle school students.

Deep infiltrating endometriosis(DIE)is defined as endometriotic lesions infiltrating≥5 mm beneath the peritoneum,commonly affecting the uterosacral ligaments,rectovaginal septum,vaginal vault,and rectal wall.Due to nonspecific clinical manifestations and atypical imaging features,DIE is often misdiagnosed.This study reports a case of rectal DIE diagnosed preoperatively by endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)and summarizes the multidisciplinary treatment experience in conjunction with a literature review.A 35-year-old woman was admitted for defecation difficulty.MRI and EUS-FNA confirmed rectal DIE.After multidisciplinary team(MDT)evaluation involving colorectal,gynecologic,and urologic specialists,laparoscopic resection of the rectal lesion,sigmoid-rectal anastomosis,and protective ileostomy were performed.Pathology confirmed rectal DIE with negative margins.The stoma was successfully reversed 4 months later,and no recurrence was observed during 21 months of follow-up.These findings highlight the pivotal role of EUS-FNA in early diagnosis and demonstrate that an MDT approach led by colorectal surgeons can significantly enhance surgical safety and completeness,providing valuable guidance for the individualized management of complex pelvic endometriosis.

Objective:To evaluate cerebrospinal fluid (CSF) flow dynamics and volume changes of pulsatile tinnitus (PT) patients induced by sigmoid sinus wall dehiscence (SSWD) using MRI.Methods:This was a cross-sectional study. Totally 55 SSWD-PT patients, and 35 age- and sex-matched healthy controls were prospectively enrolled at Beijing Tongren Hospital, Capital Medical University from October 2019 to September 2023. The CSF at the midbrain aqueduct level was analyzed based on phase-contrast MRI to obtain the flow dynamics information. Based on T 1-weighted turbo field echo sequence, the CSF was segmented and the volume of CSF was calculated using ITK-SNAP software. The Mann-Whitney U test was used to compare the differences of each parameter between the two groups. Binary logistic regression was used to analyze the parameters with statistically significant differences to obtain the independent influencing factors of SSWD-PT and establish the combined parameters. Receiver operating characteristic curve analysis was used to evaluate the efficacy of diagnosing SSWD-PT. Results:Compared with controls, the SSWD-PT group showed significantly decreased mean flux (MF), mean velocity, peak velocity( P<0.05), and significantly increased regurgitant fraction (RF), CSF volume ( P<0.05). No significant differences were observed in forward flow volume, backward flow volume, and stroke volume ( P>0.05). The logistic regression results showed that MF ( OR=0.497, 95% CI 0.305-0.808, P=0.005) and RF ( OR=1.809, 95% CI 1.040-3.147, P=0.036) were independent influencing factors of SSWD-PT. The area under the curve (AUC) of MF and RF for diagnosing SSWD-PT were 0.641 (95% CI 0.517-0.766) and 0.675 (95% CI 0.564-0.786), respectively. The AUC of the combination of MF and RF was 0.724 (95% CI 0.614-0.833). Conclusions:SSWD-PT patients have abnormal changes in CSF flow dynamics and volume. The MF and RF demonstrate moderate diagnostic value for diagnosing SSWD-PT.

Deep infiltrating endometriosis(DIE)is defined as endometriotic lesions infiltrating≥5 mm beneath the peritoneum,commonly affecting the uterosacral ligaments,rectovaginal septum,vaginal vault,and rectal wall.Due to nonspecific clinical manifestations and atypical imaging features,DIE is often misdiagnosed.This study reports a case of rectal DIE diagnosed preoperatively by endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)and summarizes the multidisciplinary treatment experience in conjunction with a literature review.A 35-year-old woman was admitted for defecation difficulty.MRI and EUS-FNA confirmed rectal DIE.After multidisciplinary team(MDT)evaluation involving colorectal,gynecologic,and urologic specialists,laparoscopic resection of the rectal lesion,sigmoid-rectal anastomosis,and protective ileostomy were performed.Pathology confirmed rectal DIE with negative margins.The stoma was successfully reversed 4 months later,and no recurrence was observed during 21 months of follow-up.These findings highlight the pivotal role of EUS-FNA in early diagnosis and demonstrate that an MDT approach led by colorectal surgeons can significantly enhance surgical safety and completeness,providing valuable guidance for the individualized management of complex pelvic endometriosis.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Analgesia is an important link in the treatment of severe patients after neurosurgery and plays a vital role in improving the prognosis of the patients.Understanding the status quo and influencing fac-tors of pain in severe patients after neurosurgery helps to predict the occurrence of pain,which is crucial for determining the new pain assessment methods and auxiliary analgesic methods and developing novel analgesic drugs.This paper reviews the pain status,pain evaluation and analgesic methods of severe patients after neuro-surgery in recent years so as to understand the pain management current status of the patients with severe neurological conditions and provide reference for the medical staff to implement the analgesic programs.

Cognitive impairment refers to the abnormality of the hippocampus， cortex and other parts of the brain， which is manifested by the decline of cognitive abilities such as learning， memory and attention. With the increase in people's work pressure and bad living habits， the incidence of cognitive impairment is getting higher and higher， which seriously affects people's normal life. However， there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore， the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine （TCM） has the characteristics of "multi-component， multi-pathway and multi-target"， and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress， inflammation， apoptosis， autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt） signal pathway plays an important role in the transmission of intracellular and intracellular signals， and in the regulation of cellular inflammation， apoptosis， autophagy， etc. TCM monomers， TCM extracts， and TCM compounds exert anti-inflammatory， antioxidant， anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway， and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress， inflammation， apoptosis and autophagy of neurons. Finally， the recent research status of the regulation of this signaling pathway by TCM extracts， TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.