Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Cerebral ischemia-reperfusion injury （CIRI） has a very high incidence， disability， and mortality rates， which seriously affects human life and health. In recent years， modern medicine has made some progress in the diagnosis and treatment of CIRI， but there are still problems such as difficulties in postoperative rehabilitation and adverse drug reactions， and new therapeutic drugs for CIRI are urgently needed. As an important class of active ingredients in traditional Chinese medicine， flavonoids can play antioxidant， apoptosis inhibition， anti-inflammatory， and other pharmacological effects to improve brain tissue damage， which is important for improving the quality of life of CIRI patients and slowing down the aging of the social population. Numerous studies have found that flavonoids in traditional Chinese medicine can regulate cell surface receptors Toll-like receptor 4/nuclear factor-kappaB （TLR4/NF-κB）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， adenylate-activated protein kinase/mammalian target of rapamycin protein （AMPK/mTOR）， Ras homologous gene family member A/Rho-associated coiled-coil protein kinase （RhoA/ROCK）， nuclear factor E₂-associated factor 2/Kelch-like epoxychloropropane-associated protein-1/haemoglobin oxygenase 1 （Nrf2/Keap1/ HO-1）， Notch， and other signaling pathways， so as to regulate the transcription and expression of related proteins after CIRI， alleviate brain tissue injury， and improve CIRI. This paper analyzed the relevant literature in China and abroad in recent years， reviewed the mechanism of action and related pathways of flavonoids in traditional Chinese medicine to improve CIRI， and explored the new therapeutic direction of CIRI at the metabolic level， with a view to providing a basis for the further development and application of flavonoids in traditional Chinese medicine.

Objective:To investigate the predictive value of a radiomics model based on biparametric magnetic resonance imaging(bpMRI)for biochemical recurrence(BCR)after radical prostatectomy(RP)in elderly prostate cancer patients(≥60 years old).Methods:A retrospective analysis was conducted on data from 175 patients treated at Beijing Hospital from August 2017 to December 2021.Based on pathological results, image segmentation was performed on preoperative bpMRI T2, diffusion weighted imaging(DWI), and apparent diffusion coefficient(ADC)sequences.Pyradiomics was utilized to extract radiomic features, and Cox regression, Spearman correlation coefficient, and LASSO regression were employed for feature dimensionality reduction, leading to the construction of radiomic labels.Clinical models and image-clinical combined models were developed using multifactorial Cox regression analysis, and the performance of these models in predicting BCR was evaluated using the concordance index(C-index).Results:The 175 patients were randomly divided into a training set(122 cases)and a test set(53 cases)at a ratio of 7∶3, with 24 cases(19.7%, 24/122)and 11 cases(20.8%, 11/53)experiencing BCR, respectively.A total of 5 775 radiomic features were extracted from the three sequences, and after dimensionality reduction, 5 features were selected to construct the radiomic labels.The radiomics model exhibited C-index values of 0.764(95% CI: 0.655-0.872)and 0.769(95% CI: 0.632-0.906)in the training and test sets, respectively.Multifactorial Cox regression analysis revealed serum prostate-specific antigen(PSA)( HR=1.032, 95% CI: 1.010-1.054), postoperative pathology International Society of Urological Pathology(ISUP)grade grouping( HR=1.682, 95% CI: 1.039-2.722), and positive surgical margins( HR=2.513, 95% CI: 1.094-5.774)as independent predictors of BCR.The clinical model exhibited C-index values of 0.751(95% CI: 0.655-0.846)and 0.753(95% CI: 0.630-0.877)in the training and test sets, respectively.Following combined modeling of clinical factors and radiomic labels, the image-clinical combined model demonstrated the highest C-index values, namely 0.782(95% CI: 0.679-0.874)and 0.801(95% CI: 0.677-0.915)in the training and test sets, respectively. Conclusions:The radiomics model based on bpMRI can predict the occurrence of BCR after RP in elderly prostate cancer patients.Combined modeling of clinical factors and radiomic labels can enhance predictive efficiency.

Stroke， including ischemic stroke and hemorrhagic stroke， has the characteristics of high morbidity， high disability rate， high mortality rate， high recurrence rate， and high economic burden. Ischemic stroke is the most common type of stroke， which is mainly caused by intracranial artery occlusion. The clinical manifestations of patients are hemiplegia， aphasia， sensory disturbance， and other neurological deficits， accompanied by gastrointestinal symptoms such as constipation and gastrointestinal bleeding. Intestinal flora plays an important role in the pathogenesis of ischemic stroke， and its potential biological effects have received extensive attention. Intestinal flora can not only affect intestinal barrier function but also regulate gastrointestinal immunity and affect host homeostasis. In recent years， traditional Chinese medicine （TCM） has shown remarkable effects and small adverse reactions in the prevention and treatment of cerebral ischemia. The research on the effect of TCM in improving cerebral ischemia injury by regulating the structure and metabolism of intestinal flora and maintaining the function of intestinal flora has gradually become a hot topic. Based on the interaction between TCM and intestinal flora in relevant literature in recent years， this review investigated the mechanism of anti-cerebral ischemic injury of TCM via regulating intestinal flora structure， affecting intestinal flora metabolism， and regulating body immunity and made a summary， proving a basis for further elucidating the role of intestinal flora in cerebral ischemia and the mechanism of TCM in prevention and treatment of ischemic stroke.

Objective To explore the predictive value of cardiopulmonary exercise test (CPET) combined with clinical indexes in the postoperative complications. Methods The clinical data and CPET data (including lung function) of patients undergoing radical esophagectomy in Xuzhou Central Hospital from January 2018 to March 2022 were collected. Univariate analysis and multivariate logistic regression analysis were used to analyze the meaningful evaluation index for the occurrence of postoperative complications. Results A total of 77 patients with esophageal cancer were included, including 59 (76.6%) males and 18 (23.4%) females aged 47-80 years. There were 42 (54.5%) patients in the non-complication group and 35 (45.5%) patients in the complication group. Univariate analysis results showed that the occurrence of postoperative complications was significantly correlated with age, body mass index (BMI), smoking index, tumor stage, the length of postoperative hospital stay, peak work rate (WRpeak), peak kilogram oxygen uptake (VO2peak/kg), the ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope), forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and maximum expiratory flow rate (MMEF) (P<0.05). The results of multivariate logistic regression analysis showed that BMI [OR=1.35, 95%CI (1.03, 1.77), P=0.031], peakVO2/kg [OR=0.64, 95%CI (0.45, 0.93), P=0.018], oxygen uptake-anaerobic threshold (ATVO2) [OR=0.66, 95%CI (0.44, 0.98), P=0.044] and VE/VCO2 slope [OR=1.49, 95%CI (1.10, 2.02), P=0.011] were the related indexes of complications after radical resection of esophageal cancer. The sensitivity of BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope in predicting postoperative complications was 82.10%, and the specificity was 87.44%, 95%CI (0.744, 0.955). Conclusion BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope can be used as predictors for postoperative complications of esophageal cancer.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To investigate the application value of MRI three-dimensional reconstruction techniques in the identification of offending vessels and affected nerves in cranial neurovascular compression syndrome.Methods A total of 91 patients with trigeminal neuralgia and 72 patients with hemifacial spasm underwent FIESTA and TOF-MRA scanning before microvascular decompression.Two-dimensional and three-dimensional reconstruction techniques(curved planar reconstruction and MR virtual endoscopy)were respectively performed using the original MRI data so as to evaluate the number and category of offending vessels and the degree of compression on cranial nerves.The results of imaging diagnosis were compared with the observations during neurosurgery.Results The correct identification rate of the offending vessels in trigeminal neuralgia was 95.6％by 3D reconstruction technique,with 94.5％diagnostic accuracy of neurovascular compression.In addition,the accurate identification rate was 91.7％on the detection of the offending vessels in hemifacial spasm,with 89.5％accuracy of the judgment on neurovascular compression.It should be noted that the diagnostic accuracy for the simple contact between the offending blood vessels and the cranial nerves using 3D reconstruction was significantly higher than that of the evaluation through 2D observation(P＜0.05).Conclusion 3D reconstruction technique can improve the accuracy of offending blood vessels identification and provide more reliable information on the degree of cranial nerve distortion or atrophy.Therefore,3D MRI images are more suitable for investigating the complex neurovascular compression.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.