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.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

As a complex and large microbial community colonized in the human body, the intestinal flora and its metabolites short-chain fatty acids (SCFAs) play an important role in participating in human metabolism, resisting pathogens, and regulating immune mechanisms. In recent years, many studies have found that the intestinal flora is closely related to bone metabolism. The intestinal flora is able to regulate bone metabolism and affect bone mass changes through various pathways such as absorption of nutrition, generation of SCFAs, regulation of immunity, and influence on body metabolism. The potential pathways and mechanisms by which intestinal flora affect bone mass changes were reviewed in this article in bone metabolism. The related study on Traditional Chinese Medicine that has effects in balancing intestinal flora for regulating bone metabolism was also introduced in order to provide new ideas for the prevention and treatment of osteoporosis, a disease related to bone metabolism.

Objective:To explore the potential genetic causes of unexplained neonatal encephalopathy.Methods:This retrospective study enrolled 113 infants diagnosed with unexplained neonatal encephalopathy and underwent genetic testing in the Children's Hospital of Hunan Province from January 2019 to May 2021. Perinatal data, clinical manifestations, electroencephalograph, brain MRI findings, genetic information, and prognosis of those patients were analyzed. T-test or Chi-square test were used for data analysis. Results:Of the 113 infants enrolled, 74 (65.5%) were males. The gestational age at birth was (38.6±1.5) weeks, and the birth weight was (2 957±561) g. The most common clinical manifestation was the disturbance of consciousness (83/113, 73.5%), followed by seizures (39/113, 34.5%). There were 38.2% (34/89) of the patients with abnormal brain MRI, and 80.4% (74/92) presented abnormal electroencephalography. Among the 113 infants, 60 (53.1%) had genetic abnormalities, including 48 with single nucleotide variations, eight with copy number variations, and four with chromosome abnormalities. Single nucleotide variations in the 48 patients were classified into syndromic ( n=18, 37.5%), metabolic ( n=16, 33.3%), epileptic ( n=11, 22.9%) and mitochondrial-related genes ( n=3, 6.3%), of which 14 were not included in any database. Among the 103 cases which were successfully followed up until December 31, 2021, 75 (72.8%) had a poor prognosis, including 52 (50.5%) death cases and 23 (22.3%) cases of development retardation. Birth weight and the incidence of seizures in the poor prognosis group were both lower than those in the non-poor prognosis group [(2 876±536) vs (3 254±554) g, t=3.15; 29.3% (22/75) vs 53.6% (15/28), χ2=5.20; both P<0.05], while the incidence of disturbance of consciousness was higher [80.0% (60/75) vs 53.6% (15/28), χ2=7.19, P<0.05]. The proportion of infants with genetic abnormalities in the poor prognosis group was higher than that in the non-poor prognosis group, but the difference was not statistically significant [53.3% (40/75) vs 46.4% (13/28), χ2=0.39, P=0.533]. Conclusions:Genetic abnormality is one of the leading causes of unexplained neonatal encephalopathy. Nucleotide variation is the most common genetic type. Syndromic, metabolic, and epileptic variants are frequently detected in these patients.

Objective To observe the effects of transnasal humidified rapid-insufflation ventilatory exchange(THRIVE)on gastric air intake and SpO2 in patients with painless endoscopic mucosal resection(EMR)of colorectal polyps.Methods Seventy patients with painless colorectal polyps EMR,36 males,34 females,aged 18-64 years,BMI 18-25 kg/m2,ASA Ⅰ or Ⅱ.The patients were divided into two groups:high-flow oxygen inhalation group(group T)and conventional oxygen inhalation group(group C)by random number table method,35 cases in each group.Patients in group T were given THRIVE oxygen inhalation,and patients in group C were routinely inhaled oxygen through the nose.During anesthesia,the BIS value was maintained at 50-65.Bedside gastric ultrasonography was used to observe the gastric content and gastric air intake of patients.The HR and resting SpO2 in the supine position were recorded 5 minutes before the surgery(rest for 5 minutes),1 minute after entering the endoscope,when entering the endoscope to the ileocecal valve,and at the end of the surgery.The PaCO2,PaO2 and pH values were recorded 5 mi-nutes before surgery,when entering the endoscope to the ileocecal valve,and at the end of the surgery,so were gastric intake and satiety,and antral cross-sectional area(CSA)for 5 minutes before surgery and after surgery.The occurrence of mild,moderate,and severe hypoxia during anesthesia were recorded.The opera-tion time,the amount of propofol used during the operation,the number of dosage times of remifentanil,PACU residence time,and infusion during surgery,the occurrence of adverse reactions such as hypotension,hypertension,bradycardia,reflux aspiration,postoperative nausea and vomiting,and the sat-isfaction score of digestive endoscopy physicians and patients were recrded.Results Compared with group C,SpO2 in group T was significantly increased 1 minutes after entering the endoscope(P＜0.05),and PaCO2 was significantly decreased at the time of entering the endoscope to the ileocecal valve and the end of the surgery(P＜0.05),the incidence of mild and moderate hypoxia was significantly reduced in group T(P＜0.05).No positive gastric air intake and full stomach were found in both groups at rest for 5 minutes and after the surgery.There was no significant difference in the incidence of adverse reactions and patient satisfaction scores between the two groups.The satisfaction score of endoscopists in group T was significantly higher than that in group C(P＜0.05).Conclusion Compared with conventional nasal catheter oxygen inhalation,THRIVE ventilation does not cause hypercapnia or affect gastric intake and stomach content,does reduce the occurrence of mild to moderate hypoxia in patients undergoing painless EMR,does not in-crease the risk of reflux aspiration,and has a higher satisfaction of digestive endoscopy physicians.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective：To analyze the expression and clinic significance of activity-dependent neuroprotective protein (ADNP) in bladder urothelial carcinoma. Methods: A total of 28 pairs of bladder cancer tissues and corresponding adjacent normal tissuesthat surgically resected at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from June 1, 2019 to July 15, 2019 were collected for this study. The mRNAexpression ofADNP in 20 pairs of tissue samples was detected by qPCR, and the protein expressionin the other 8 pairs was detected by WB. Mean while, the clinicopathological data of patients with bladder urothelial carcinoma treated in our hospital from January 1, 2005 to December 31, 2007 were retrospectively analyzed; and the expression of ADNP in the corresponding paraffin tumor sections were determined with immunohistochemical staining, and normal bladder tissue sections from patients who underwent surgery for other bladder diseases during the same period were collected for comparison. Chi-square test was used to analyze the correlation between ADNP expression and different clinicopathological features, Kaplan-Meier method was used for survival analysis, and Cox risk regression model was used forunivariate and multivariate analysis of prognosticfactors. Results: ThetranscriptionalandtranslationallevelsofADNPincancertissues were higher than those in adjacent normal tissues (all P<0.05), and the expression level ofADNP was correlated with the histological grade, clinical stages and survival status of patients with bladder cancer (P<0.05). Of all the 221 patients included in the study, 32 patients lost to follow-up,and patients with high ADNP expression had

To explore roles of expressions of EHD2 and E-cadherin in clear cell renal cell carcinoma (ccRCC).
 Methods: Four couples of fresh ccRCC tissues and adjacent non-cancerous tissues were collected to evaluate the expression of EHD2 and E-cadherin protein by Western blotting. A total of 65 paraffin-embedded renal ccRCC tissues were collected, and immunohistochemical assay was used to detect the expression of EHD2 and E-cadherin in the samples. The correlation between their expression and clinical and pathological indicators of ccRCC was analyzed, and the relationship between EHD2 and E-cadherin proteins and prognosis for patients with ccRCC was also explored.
 Results: The results of Western blotting showed that the expression levels of EHD2 and E-cadherin were low in 4 ccRCC tissues compared with the adjacent noncancerous tissues. Immunohistochemical results revealed that the expressions of EHD2 and E-cadherin were higher in the localized ccRCC tissues than those in the metastatic ccRCC tissues; the expression levels of EHD2 and E-cadherin were decreased, while the TNM staging and Fuhrman grade were increased (P<0.05 or P<0.01). There was positive correlation between the expressions of EHD2 and E-cadherin in ccRCC (r=0.390, P<0.01). The progression-free survival in ccRCC patients with lower expression of both EHD2 and E-cadherin was better than that in ccRCC patients with higher expressions of EHD2 and E-cadherin (P<0.05). 
 Conclusion: The low expressions of EHD2 and E-cadherin are the potential indicators for the ccRCC patients with poor prognosis.
Cadherins ; Carcinoma, Renal Cell ; Carrier Proteins ; Humans ; Kidney Neoplasms ; Neoplasm Staging ; Prognosis

Objective To investigate the characteristics and clinical significance of ocular vestibular evoked myogenic potential (oVEMP) and caloric test in Meniere disease (MD) at different hearing stages.Methods Fifty-five patients(52.8±15.8 years old) with MD were divided into stage 1(9 cases,48.8±13.8 years old), stage 2(9 cases,46.0±16.3 years old), stage 3(23 cases,50.3±13.5 years old) and stage 4(cases 14, 53.5±16.2 years) respectively according to the pure tone audiometry.They were evaluated by oVEMP and caloric test.Results The abnormal rates of oVEMP were 55.6%, 66.7%, 78.3%, 78.6%,and caloric tests were 22.2%, 33.3%, 78.3%,and 85.7% respectively in stage 1, 2, 3, and 4 MD patients.The amplitudes of oVEMP in stage of 1, 2, 3, and 4 MD patients were 4.3±4.0 μV,3.5±2.3 μV,2.5±2.4 μV,and 1.3±0.5 μV,respectively.Conclusion The abnormal rates of oVEMP and caloric tests in MD patients increased with the degree of hearing impairment and the amplitudes of oVEMP were decreased, suggesting that utricle and horizontal semicircular canal injuries were aggravated.

Objective To study the clinical features and follow-up of newborns with severe hypoxic-ischemic encephalopathy ( HIE) , and to provide the basis for rational diagnosis, treatment and follow-up.Methods Clinical data of cases of HIE from the Neonatal Department of our Hospital from January 2011 to October 2014 were studied retrospectively. The data of general information, laboratory examination, treatment, outcome, follow-up and prognosis of the patients were collected. Multivariate logistic regression analysis was used to study the influential factors of the prognosis of HIE.Results A total of 123 infants with sever HIE were enrolled in our study. In addition to general therapy, 6 cases were treated with mild hypothermia, and 21 cases were treated with high pressure oxygen. 60 cases improved our treatment, 55 cases had withdrawal treatment with parental consent, and 8 cases died. Single factor analysis showed that 5 minutes Apgar score, convulsions, coma, pH, BE, organ injury, and mild hypothermia treatment were the risk factors that affect the prognosis of severe HIE. Multiple factors analysis showed that 5 min Apgar score <3 points ( OR=4. 071 ,95℅CI 1. 309-15. 613 ) and BE≤-10 mmol/L ( OR=36. 810, 95℅CI 5. 913-41. 119) were independent risk factors of prognosis of severe HIE ( P<0. 05). Hospitalization within the first 72 hours of life ( OR=0. 096, 95℅CI 0. 096-0. 353) was a protective factor of severe HIE. Multiorgan injury ( mainly the injury of brain, lung and heart) and electrolyte imbalance ( mainly hypocalcemia and hyponatremia ) were common complications of serve HIE. In the follow-up of these patients, 33 cases were loss in follow up, and 49 cases died (8 cases died during hospitalization, 41 cases died after withdrawal of treatment). The top five causes of death were abandonment of treatment due to financial reasons and the fear of adverse outcome (n=20), multiple organ dysfunction ( n =16 ) , and pneumothorax ( n =4 ) , diffuse intravascular coagulation (n=6), and shock (n=3). 41 cases survived were followed up for 9~54 months. The critical clinical conditions observed among these infants included cerebral palsy ( n = 5 ) , epilepsy ( n = 3 ) and developmental retardation(n=26).Conclusions There are many complications of severe HIE.The mortality of severe HIE is high, and the incidence of poor outcome of survivors is also high. Timely detection of risk factors is the key to the prevention of severe HIE. Long-term prognosis of severe HIE requires proper organization of neonatal follow up.