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 payment methods,such as Diagnosis Related Group(DRG)for hospitalization and capitation for outpatient treat-ment,have achieved positive results in protecting the rights and interests of insured persons and improving the efficiency of the use of medical insurance funds.However,for patients with chronic diseases and rehabilitation nursing,the hospitalization period is long and the conditions complicated,and the payment method of DRGs is not reasonable.It analyzes the experiences of paying for long-term hospital cases in the US.and Germany from the aspect of reform process,payment method and regulatory measures.In order to pro-vide references for the reform of per-diem payment in rehabilitation nursing and other long-term hospitalized cases,it puts forward suggestions from aspects of realizing value care,reflecting individual differences,exploring complex payment methods,improving data quality and establishing constraint mechanism.

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.

AIM: To compare the clinical effectiveness of using multifocal defocus spectacle lenses, orthokeratology lenses, and single-vision spectacle lenses in patients with myopia and small-angle intermittent exotropia.METHODS: This retrospective study included 150 patients aged 8-15 years with basic intermittent exotropia, strabismus of -10△ to -20△ prism diopters(D)(block lenses), and spherical equivalents of -1.00 to -5.50 D, who visited our hospital from June 2021 to September 2022. They were selected and divided into three groups on a voluntary basis: the HAL group(50 patients with multifocal myopia defocus spectacle lenses), the OK lens group(50 patients with nighttime orthokeratology lenses), and the SVL group(50 patients with regular single-vision spectacle lenses). After wearing the lenses consistently, changes in axial length, prism diopters with the naked eye and lenses(prism at 33 cm), positive fusional vergence of blurred points, and near stereopsis were observed and compared among groups before intervention and after 1 a. The Newcastle control score(NCS)was used to evaluate the eye position control ability of the patients in the three groups.RESULTS: Before the intervention, the axial lengths of the HAL, OK lens, and SVL groups were 24.83±0.91, 24.93±0.97, and 24.98±0.68 mm, respectively(P>0.05). After 1 a, the axial lengths of the three groups were 25.02±0.90, 25.18±0.97, and 25.45±0.65, respectively(P<0.05). Compared with an increase of 0.47±0.30 mm in the SVL group after 1 a, the axial length of the HAL and OK lens groups increased by 0.19±0.06 and 0.25±0.21 mm, respectively(both P<0.05). Before intervention, the prism diopters of the HAL, OK lens, and SVL groups measured using the prism were -15.00△±3.12△, -14.34△±3.00△ and -14.06△±3.22△, respectively. After 1 a, the prism diopters of the three groups with lenses were -9.34△±3.84△, -18.42△±4.41△, and -19.58△±5.21△, respectively, which increased by 5.66△±2.13△, -4.08△±3.34△, and -5.52△±3.70△, respectively, compared with the preintervention values(P<0.05). Before intervention, the near stereopsis in the HAL, OK lens, and SVL groups were 89.20″±54.65″, 93.00″±52.54″, and 88.40″±55.31″, respectively(P>0.05). After 1 year, near stereopsis in the groups were 76.00″±20.40″, 81.20″±18.91″, and 100.60″±51.41″, respectively(P<0.05). The positive fusional vergence(fuzzy point)of the three groups was 15.04±1.97, 15.14±1.67, and 14.62±1.47, respectively, before intervention(P>0.05), and it was 17.10±2.02, 13.12±1.41, and 13.26±2.45, respectively, after 1 a(P<0.05). In addition, the eye position control in the HAL group was significantly better than that in the OK lens and SVL groups after wearing lenses for 1 a(P<0.05).CONCLUSION: For patients with myopia and small-angle intermittent exotropia, wearing HAL can effectively control changes in strabismus and axial length compared with OK lenses and SVL, particularly for better control of strabismus, whereas wearing OK lenses or SVL would result in exotropic drifts. Stereopsis and positive fusional vergence were significantly improved in the HAL group.

Objective To explore the effect of taking silicone oil at different time points in intestinal preparation.Methods A total of 330 patients who underwent colonoscopy at the First Affiliated Hospital of Wenzhou Medical University from January to December 2022 were selected as the study subjects.The patients were divided into three groups according to random number method,namely,A,B,and C,with 110 patients in each group.Group A patients received silicone oil 1 hour before colonoscopy,Group B received silicone oil 2 hours before colonoscopy,and Group C received silicone oil 4 hours before colonoscopy.Compare the score of air bubbles in the intestinal lumen,the amount of saline irrigation,and the satisfaction of the surgeon in the operation among the three groups of patients.Results There were statistically significant differences among the three groups in the content of air bubbles in the intestinal lumen,the amount of saline irrigation,and the satisfaction of the surgeon with the procedure(P<0.05).But group B has the best results.Conclusion Oral administration of silicone oil 2 hours before colonoscopy can significantly reduce air bubbles in the intestinal lumen,improve the clarity of the observation field of colonoscopy,and improve the satisfaction of the operating physician.

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.

The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans responded to the new issues faced by ethical review arising from the development of science and technology,society,and ethics,as well as the requirements of laws and regulations for ethical review.It adapted to the continuous increase of investment in scientific and technological innovation research and the development of biotechnology in China,and expanded the applicable institutions and research types of the ethical review system.Facing the ethical review of life sciences and medical research involving humans is one of the practical forms of responsible research and innovation.Therefore,it is necessary to establish and improve the ethical review system,implement the"subject responsibility"of life sciences and medical research involving humans,carry out classified and hierarchical bioethics education,and enhance the consciousness of researchers,research managers,and students in responsible research and innovation.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.