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.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE To evaluate the long-term cost-effectiveness of insulin degludec and insulin aspart （IDegAsp） in patients with type 2 diabetes mellitus （T2DM） in China. METHODS A cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system， using the CORE diabetes model to simulate long-term （20-year） health and economic outcomes. Baseline cohort characteristics and treatment effect data were derived from the CREATE study. The prices of glucose- lowering drugs were obtained from medical insurance payment standards and the average winning bid prices in the follow-up round of the specialized centralized procurement for insulin， while the daily dosages were derived from the CREATE study. The costs of complications and utility values were obtained from published literature， with a discount rate of 5%. One-way sensitivity analysis， scenario analysis， and probabilistic sensitivity analysis were performed to verify the robustness of the results. RESULTS Patients switching from previous once-daily basal insulin regimens to IDegAsp therapy gained an incremental 0.190 quality-adjusted life year （QALY） with direct medical cost savings of 42 163.58 yuan. For those switching from premixed insulin therapies， IDegAsp treatment provided 0.130 incremental QALY and reduced direct healthcare costs by 41 129.11 yuan. The outcome was significantly influenced by the discount rate and the cost of complications. Probabilistic sensitivity analysis and scenario analysis confirmed the robustness of these findings. CONCLUSIONS Switching from previous daily basal insulin or premixed insulin regimens to IDegAsp in Chinese patients with T2DM can improve patients’ long-term health outcomes and achieve cost savings， making it a more cost-effective treatment option.

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.

BACKGROUND:Transcranial magneto-acoustical electrical stimulation(TMAES)is a non-invasive,high-precision neurofocused stimulation method based on magneto-acoustic coupling electrical effect,which can regulate the rhythmic oscillation of nerve activity,thereby affecting the brain's movement,cognition and other functions. OBJECTIVE:To explore the effect of TMAES on beta oscillations in the neural circuits of healthy rats and Parkinson's rats. METHODS:(1)Animal experiments:Twenty-four Wistar rats were randomly divided into four groups(n=6 per group).The rats in the normal control group received no intervention,while those in the normal stimulation group received TMAES(the average spatial peak pulse intensity:13.33 W/cm2,fundamental frequency:0.4 MHz,the number of fundamental wave cycles:1000,and pulse frequency:200 Hz).The model control group and model stimulation group were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.After successful modeling,the rats in the model control group received sham TMAES stimulation in the prefrontal cortex,and those in the model stimulation group received TMAES in the prefrontal cortex,and the duration of stimulation was 2.0 minutes per day.After an interval of 8-10 minutes,the local field potential signals of rats were collected during the execution of T-maze test and the correct rate of behavior was recorded at the same time to compare and analyze the time-frequency distribution of local field potential signals and behavioral differences among the groups.The stimulation experiment and T-maze test were stopped when the correct rate of rats was higher than 80%for 3 consecutive days.(2)Modeling and simulation experiments:The cortical-basal ganglion circuit model under TMAES was established,and the ultrasonic emission period(5,10,20 ms),ultrasonic emission duty cycle(30%,50%,90%)and induced current density(20,50,100 μA/cm2)were changed respectively to compare the power spectral density values of beta oscillations in healthy rats and Parkinson's rats under different stimulation parameters. RESULTS AND CONCLUSION:(1)Animal experiments:The spatial learning ability of the rats in the normal control group was stronger than that of the model control group(P＜0.001),the spatial learning ability of the rats in the normal stimulation group was stronger than that of the normal control group(P＜0.05),and the spatial learning ability of the rats in the model stimulation group was stronger than that of the model control group(P＜0.01).The distribution of beta oscillation energy in the normal control group was more concentrated,and the beta oscillation signal energy was reduced in the normal stimulation group compared with the normal control group.The beta oscillation energy was widely distributed and the energy value was significantly higher in the model control group and the model stimulation group than the normal control and normal stimulation groups.Moreover,the beta oscillation signal energy in the model stimulation group was significantly lower than that in the model control group.(2)Modeling and simulation experiments:the peak power spectral density of the beta band of healthy rats without stimulation(30 dB)was significantly lower than that of Parkinson's rats(55 dB).The power spectral density value generally decreased after stimulation.The peak power spectral density in the beta band was positively correlated with the ultrasonic emission period and negatively correlated with the induced current density.In addition,the peak power spectral density value was the lowest when the duty cycle of ultrasonic emission was 50%.These findings indicate that TMAES suppresses beta oscillations in healthy and Parkinson's disease rats,thereby improving motor function and decision-making cognitive function in rats.