Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.

Objective To study the the expression of cytokeratin 5/6(CK5/6)and cell proliferation an-tigen(Ki-67)in apocrine triple-negative breast carcinoma(ATNBC)and their relationship with clinicopatho-logical features and prognosis.Methods Twenty-one patients with pathologically diagnosed invasive apocrine breast cancer and negative estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor-2(Her-2)in this hospital were selected as the ATNBC group,Twenty-two cases in non-ATNBC(NATNBC)were randomly selected as negative control(NATNBC group).The clinical pathological data and follow-up data of all patients were collected,and the expressions of CK5/6 and Ki-67,as well as their relation-ship with clinicopathological characteristics was analyzed.The prognosis in the patients with ATNBC was ana-lyzed.Results There were statistically significant differences in age(P＜0.001),age distribution(P=0.001),histological grading(P＜0.001),and distant metastasis(P=0.020)between the ATNBC group and the NATNBC group(P=0.020).There were 7 cases(33.33％)of CK5/6 positive expression in the ATNBC group and 17 cases(80.95％)in NATNBC group.There was statistically significant difference in the positive expression rate of CK5/6 between the ATNBC group and NATNBC group(P＜0.05).There were 3 cases(14.29％)of Ki-67 high proliferation in the ATNBC group and 17 cases(77.27％)in the NATNBC group.The high proliferation rates of Ki-67 had statistically significant difference between the ATNBC group and NATNBC group(P＜0.05).The positive expression rate of CK5/6 was correlated with the tumor sites and lymph node metastasis in ATNBC patients(P＜0.05).The high proliferation rate of Ki-67 was correlated with nerve invasion in ATNBC patients(P＜0.05).The survival analysis showed that there was statistically significant difference in the 5 years disease-free survival(DFS)rate between the ATNBC group and NATNBC group(P＜0.05).Conclusion ATNBC has its unique clinicopathological features,CK5/6 is less expressed in ATN-BC,the high proliferation of Ki-67 is also less,and the prognosis of ATNBC is better than that of NATNBC.

Diagnostic criteria, as a critical component of clinical practice guidelines, play a direct role in guiding clinicians' diagnostic and treatment decisions. Although China has increasingly emphasized the development and updating of clinical guidelines in recent years, research focusing on the diagnostic criteria within these guidelines remains limited. This paper aims to explore the types of diagnostic criteria, the issues they present, and the processes involved in their formulation. Based on this analysis, suggestions are proposed to improve the recommendation and application of diagnostic criteria in Chinese guidelines.

In recent years,the infection of nontuberculous mycobacterium(NTM)has been increasing rapidly,which captivates widespread attention.The infection rate of NTM in kidney transplant recipients is more significantly elevated due to the impact of immunosuppressive drugs and other factors.However,due to the lack of sufficient research evidence,relevant guidelines for the diagnosis and treatment of NTM after kidney transplantation are still lacking.To further standardize the diagnosis and treatment of NTM disease in kidney transplant recipients,and deepen medical practitioners'understanding and diagnosis and treatment of NTM disease in organ transplantation in China,Branch of Organ Transplantation of Chinese Medical Association organized relevant experts to formulate this guideline by referring to the latest edition of"An official ATS/IDSA statement:diagnosis,treatment,and prevention of nontuberculous mycobacterial diseases","Expert Consensus on the Diagnosis and Treatment of Nontuberculous Mycobacterial Disease",and"Technical Specification for Clinical Diagnosis and Treatment of Nontuberculous Mycobacteria in Organ Transplant Recipients(2019 Edition)",and considering the characteristics of kidney transplant recipients.

BACKGROUND:Research on foot and ankle proprioception is crucial for the rehabilitation of chronic ankle instability and geriatric diseases as well as for the improvement of body posture control and motor performance.Previous studies have often studied the sensory evaluation of the foot and ankle joints separately,which has limitations for a comprehensive understanding of their sensory function. OBJECTIVE:The foot and ankle complex is the only part in direct contact with the support surface,and plays an important role in the collective sensory feedback and regulation and balance control.By combing the existing investigation and research of foot and ankle ontology,the measurement and evaluation methods of the sensation of the foot and ankle complex are combed,in order to pave the way and provide the theoretical basis for future related studies. METHODS:Chinese terms"(foot OR foot ankle OR ankle)AND(sensation OR proprioception)"and English terms"(foot OR ankle)AND(feel OR proprioception)"were used as the keywords for retrieving relevant literature in the Web of Science,PubMed,and CNKI.We understood the basic concepts,current status and scope of research on the foot and ankle,summarized and evaluated the proprioceptive evaluation methods of the foot and ankle,and finally included 57 papers for further review. RESULTS AND CONCLUSION:The evaluation of foot and ankle complex sensation was mainly divided into sensory evaluation of the foot and proprioceptive evaluation of the ankle joint.The sensory evaluation of the foot mainly describes the sensation of the skin and the sensory feedback under the intervention conditions.The methods mainly include the pressure sensory threshold test,the two-point discrimination test of the foot(planar and plantar),and the duration test of skin vibration sensation.Ankle joint proprioception evaluation focuses on the description of joint position,motion range,force value and functional performance.The methods are mainly divided into static joint angle reset test,motion minimum threshold test,force perception reproduction test and dynamic balance,speed and walking ability tests.The report of quantitative results is generally expressed by"an error,"which is generally divided into absolute error,relative error,constant error,etc.To conclude,the foot and ankle complex has specific sensory capabilities,including foot sensation and ankle proprioception,which affect the quality of life and athletic performance of humans.Weakness of both foot sensation and ankle proprioception is associated with reduced human balance,and the combined measurements of the two can comprehensively and effectively evaluate foot and ankle function.The combination of foot and ankle sensory measures is selected according to different research needs and various influencing factors such as environment,emotion and reporting style are fully considered,to improve the validity of measurement and evaluation.