Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Meropenem （MEM） is one of the important drugs for the treatment of severe infections， but the standard dose is often difficult to achieve an effective therapeutic concentration target. This article reviews the related studies on the population pharmacokinetics of MEM in patients with severe infection. It is found that the apparent volume of distribution （Vd） and clearance rate are the most important factors affecting the dose adjustment， and the factors affecting Vd include serum albumin， age， overall weight， shock status， and chest/abdomen/cerebrospinal fluid drainage. The main factors affecting the clearance rate were renal function， renal replacement therapy treatment mode and combination therapy. For adult patients with severe infections in China， MEM is recommended to be administered in an individualized manner based on glomerular filtration rate， with a dosage range of 500 to 1 500 mg given every 4 to 6 hours， and prolonged infusion is preferred. When the minimum inhibitory concentration （MIC） of the pathogenic bacteria reaches 64 mg/L， therapeutic drug monitoring is required. For therapeutic efficacy， it is essential to ensure that the trough concentration remains above the MIC； to prevent drug resistance， it should be maintained above 4×MIC. Regarding safety， it is recommended that the upper limit of the trough concentration be 32 mg/L， and blood sampling for monitoring can be conducted as early as after 1 to 2 doses of administration.

The pathogenesis of chronic sinusitis is complex, involving a variety of inflammatory cells and inflammatory mediators, and neutrophils play a key role in the pathological process of chronic sinusitis. Understanding the molecular basis of the pathogenesis of CRS is helpful for the precise diagnosis and treatment of chronic sinusitis. This article will systematically review the mechanism of neutrophils in the inflammatory response of the body, their role in the pathogenesis and treatment progress in CRS, and look forward to future research directions.
Humans ; Neutrophils ; Sinusitis/immunology* ; Chronic Disease

This article provides a comprehensive review of the progress in the application of transoral robotic surgery（TORS） in the field of head and neck surgery. It elaborates on its developmental background and technical principles as a subset of natural orifice endoscopic surgery and highlights the technical characteristics and optimization trends of both general-purpose and specialized surgical robotic platforms. The review emphasizes the key advantages of TORS in addressing the limitations of traditional transoral surgery, improving surgical precision, and expanding the scope of surgical indications. This in-depth analysis serves as a valuable reference for the future development and wider adoption of TORS technology in head and neck surgery.
Humans ; Robotic Surgical Procedures/methods* ; Natural Orifice Endoscopic Surgery/methods* ; Mouth/surgery*

OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Brother of regulator of imprinted sites (BORIS), also known as CCCTC binding factor-like (CTCFL), is a relatively newly discovered cancer-testis antigen. Drug development related to BORIS has been carried out in multiple directions, including small molecules, small RNA molecules, polypeptides, vaccines, and cellular therapies. Due to its unique ability to interfere with the higher-order spatial structure of the genome, BORIS may represent a new class of drug targets. Here we systematically review the molecular biology research results related to BORIS, including the diversity of its gene products, the multipartite interactions mediated by BORIS, the subsequent impact on signaling pathways, and current drug development strategies, in order to gain a better understanding of the molecular mechanisms of BORIS in both upstream and downstream regulation networks and to identify potential research directions for further breakthroughs.

Objective To explore the risk factors of apathy and correlations with cognitive function in patients with hypertension combined with cerebral small vessel disease(CSVD).Methods Totally 141 patients with hypertension combined with CSVD were prospectively enrolled and were divided into apathy group(n=43)and non-apathy group(n= 98)according to neuropsychiatric inventory-apathy scale(NPI-Apathy)scores.The general data,imaging marker scores and total imaging burden scores were compared between groups.In hypertension combined with CSVD patients,multivariate logistic regression analysis was performed to screen the independent risk factors of apathy,and Spearman correlation analysis was also performed to observe the correlation of apathy and cognitive function.Results The patients'age,high density lipoprotein cholesterol(HDL-C),Fazekas scores of lateral periventricular white matter hyper-intensity(WMH),cerebral microbleed of depth/infratentorial and total imaging burden scores of apathy group were all higher,while mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores were both lower than those of non-apathy group(all P＜0.05).HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy(both P＜0.05),while NPI-Apathy scores were moderately negatively correlated with cognitive function in patients with hypertension combined with CSVD(r=-0.543,-0.484,both P＜0.001).Conclusion HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy in patients with hypertension combined with CSVD.The more severe the apathy,the lower the cognitive function.

ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice. MethodMale ICR mice were randomized into normal， model， paroxetine （20 mg·kg^-1）， and low- and high-dose （3.27， 6.54 g·kg^-1， respectively） Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin （DCX） in the dentate gyrus （DG） of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/extracellular signal-regulated kinase （ERK）/cAMP-response element-binding protein （CREB） pathway in the hippocampus. ResultCompared with the normal group， the model group showed decreased sucrose preference rate， increased immobility time in the tail suspension test （P<0.01）， and reduced residence time in the central area of the open field and the total movement distance （P<0.05， P<0.01）. In addition， the modeling elevated the corticosterone level in the serum （P<0.01）， decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area， reduced the expression of DCX in the DG area， and down-regulated the protein levels of BDNF， phosphorylated （p）-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. Compared with the model group， low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference， open field， and tail suspension tests （P<0.05， P<0.01）， and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests （P<0.05， P<0.01）. In addition， Wenxiao powder lowered the serum corticosterone level （P<0.01） and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover， Wenxiao powder at both doses promoted the expression of DCX in the DG area， and high-dose Wenxiao powder up-regulated the protein levels of BDNF， p-TrkB， p-ERK， and p-CREB in the hippocampus （P<0.05， P<0.01）. ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.