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.

Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the PPM1D gene: c.1281G > A (p.Trp427Ter). This report also reviews the current literature on the clinical characteristics, diagnostic approaches, and therapeutic advances related to this condition, aiming to provide valuable insights for its clinical diagnosis and management.

Objective: To investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective To investigate the potential mechanism by which dihydromyricetin(DHM)ameliorates diabetic nephropathy(DN),and to screen and validate its possible key molecular targets.Methods A DN model was established using db/db mice,and 100 mg/(kg·d)DHM was administered via gavage 5 d per week for totally 10 weeks.Renal morphological changes were observed after staining to evaluate the effects of DHM.GSE161885 and GSE270526 datasets were obtained from the Gene Expression Omnibus(GEO)database and analyzed in combination with the GeneCards database to screen for DN-related differentially expressed genes(DEGs).Protein-protein interaction(PPI)network and molecular docking were employed to predict potential DHM targets.Western blotting and immunofluorescence staining were performed to detect the effects of DHM on pyroptosis-related pathways in the renal tissues of db/db mice and in high glucose(HG)-induced human renal tubular epithelial cells(HK-2).The specific NLR family pyrin domain containing protein 3(NLRP3)inhibitor MCC950 was also used to validate the predicted mechanism.Results In vivo experiments showed that DHM significantly ameliorated renal pathological damage in db/db mice,alleviated glomerular hypertrophy and mesangial expansion,and markedly reduced Paller scores(P<0.001).Immunofluorescence staining revealed significantly weakened fluorescence signals for α-smooth muscle actin(α-SMA),fibronectin,and collagen Ⅰ in renal tissues.Western blot results showed that the expression levels of collagen Ⅰ,collagen Ⅲ,α-SMA,and transforming growth factor beta 1(TGF-β1)were significantly decreased(P<0.05).A total of 16 DN-related DEGs were identified.Enrichment analysis revealed that these genes were primarily enriched in pathways such as viral protein interactions,cytokine-cytokine receptor interaction,and the AGE-RAGE signaling pathway in diabetic complications,and were primarily involved in gene functions such as the positive regulation of lymphocyte-mediated immunity,positive regulation of adaptive immune response,and chemokine activity.Molecular docking confirmed NLRP3 as a potential target of DHM.In vivo validation showed that DHM significantly down-regulated gasdermin-D(GSDMD)fluorescence signals and inhibited the expression of pyroptosis-related proteins including NLRP3,Caspase 1,Cleaved-Caspase 1,interleukin 18(IL-18),and GSDMD(P<0.05).In vitro studies further confirmed that both DHM and the specific NLRP3 inhibitor MCC950 alleviate high glucose-induced fibrosis and pyroptosis in HIC-2 cells.Conclusion DHM can ameliorate the progression of DN,and its mechanism is related to inhibiting NLRP3 inflammasome-mediated pyroptosis,thereby alleviating renal inflammation and fibrosis.

Objective To investigate the correlation between serum amyloid A(SAA)level and disease se-verity in children infected with severe acute respiratory syndrome coronavirus 2(COVID-19).Methods A to-tal of 116 children infected with COVID-19 admitted to the Department of Pediatrics of the hospital from De-cember 2022 to April 2023 were included and divided into asymptomatic/mild group and moderate/severe group according to the severity of the disease.In addition,65 healthy children who received health examination during the same period were selected as the control group.Serum SAA levels in children in acute stage and convalescent stage were detected by enzyme-linked immunosorbent assay.Results Compared with the control group,the serum SAA level in the children infected with COVID-19 was significantly increased in the acute stage(P＜0.05).The area under the receiver operating characteristic(ROC)curve(AUC)of SAA levels in the acute stage for diagnosing children with COVID-19 infection was 0.926(95％CI:0.886-0.966).In SARS-CoV-2 infected children,the SAA levels in the acute stage in the asymptomatic/mild group and the moderate/severe group were 2.71(1.29-10.86)mg/L and 37.78(18.58-92.62)mg/L,the differences were statistically significant between the two groups(Z=5.782,P＜0.001).In addition,serum SAA was pos-itively correlated with severity of SARS-CoV-2 by Spearman analysis(r=0.657,P＜0.001).Serum SAA lev-els were also significantly positively correlated with C-reactive protein(CRP),immunoglobulin(Ig)M,IgG,IgA and neutralizing antibody(NAb)in acute stage(P＜0.05).The AUC of serum SAA level in acute stage for diagnosing the moderate/severe children with SARS-CoV-2 was 0.889(95％CI:0.842-0.955),which was higher than that of CRP(P＜0.05).Compared with serum antibodies(IgM,IgG,IgA and NAb),the rate of serum SAA positive(≥5.55 mg/L)in children in acute stage was significantly higher(P＜0.05).The positive rate of serum SAA in convalescent children was significantly lower than that of serum antibody(P＜0.05).Conclusion Elevated serum SAA in acute phase is associated with increased risk of SARS-CoV-2 infec-tion and disease severity in children.Serum SAA is promising as a good biomarker for monitoring SARS-CoV-2 infection and severity in children.

Objective To investigate the potential of immune-inflammatory markers and the characteristics of magnetically controlled capsule endoscopy in distinguishing gastric adenocarcinoma from precancerous lesions,as well as to develop and validate a risk prediction model.Methods Retrospective analysis was conducted on medical records of 578 patients who underwent magnetic controlled capsule endoscopy at our hospital between January 2021 and December 2023.Following the principle of Pareto's law(80/20 rule),they were randomly divided into a training set(462 cases)and a validation set(116 cases).Magnetic controlled capsule endoscopy and blood cell tests were performed,with pathological diagnosis results serving as the"gold standard",to classify patients into groups of gastric adenocarcinoma and precancerous lesions.The magnetic controlled capsule endoscopic features,neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR)in patients with gastric adenocarcinoma and precancerous lesions were compared to develop and validate a risk diagnostic model for gastric adenocarcinoma.Results Among the 462 patients who underwent magnetic controlled capsule endoscopy,gastric adenocarcinoma was diagnosed in 76 cases through pathological examination,accounting for 16.45%(76/462),while precancerous lesions were observed in 386 cases,accounting for 83.55%(386/462).In the validation set of 116 patients who underwent gastric endoscopy,there were 22 cases of gastric adenocarcinoma,representing an incidence rate of 18.97%(22/116),and a total of 94 cases with precancerous lesions,accounting for an incidence rate of 81.03%(94/116).No statistically significant differences(P＞0.05)were found between the two groups regarding lesion size,border appearance,mucus presence or lesion morphology.However,compared to the precancerous lesion group,the proportion of whitish coloration as well as irregular surface microstructure and grid-like microvessels was significantly higher in the gastric adenocarcinoma group(P＜0.05).Moreover,both NLR and PLR values were significantly higher in the gastric adenocarcinoma group compared to those in the precancerous lesion group(P＜0.05).Irregular surface microstructure(OR=2.213,95%CI:1.288～3.801),irregular grid-like microvessels(OR=2.489,95%CI:1.458～4.249),NLR(OR=2.369,95%CI:1.389～4.046),and PLR(OR=3.016,95%CI:1.767～5.148)were identified as risk factors for gastric adenocarcinoma(P＜0.05).The sensitivity of the risk model for diagnosing gastric adenocarci-noma in the training set was 0.800(95%CI:0.716～0.891),with a specificity of 0.783(95%CI:0.694～0.851)and an area under the curve of 0.858(95%CI:0.787～0.931).In the validation set,the sensitivity for diagnosing gastric adenocarcinoma was 0.861(95%CI:0.771～0.945),with a specificity of 0.769(95%CI:0.683～0.841)and an area under the curve of 0.844(95%CI:0.765～0.923).Conclusion The surface microstructure,microvas-cular morphology,NLR,and PLR of gastric lesions are correlated with the occurrence of gastric adenocarcinoma.Developing a risk diagnostic model facilitates early identification and diagnosis of gastric adenocarcinoma.

ObjectiveIn order to explore the utilization value of the seeds dropped in the harvesting， processing， storage and transportation of Prunellae Spica， the character， turgidity and chemical composition of the seeds were analyzed and compared with those of the commercially available varieties， such as chia seeds and basil seeds. MethodCharacter was observed directly. The turgidity was determined according to the method of general rule 2101 of Chinese Pharmacopoeia （part Ⅳ， the 2020 edition）. The contents of six phenolic acids （danshensu， protocatechuic acid， protocatechuic aldehyde， caffeic acid， salviaflaside and rosmarinic acid） were determined by ultra performance liquid chromatography （UPLC）， acetonitrile （A）-0.1% formic acid aqueous solution （B） was used as mobile phase for gradient elution （0-7 min， 2%-8%A； 7-13 min， 8%A； 13-14 min， 8%-17%A； 14-30 min， 17%A）， the detection wavelength was at 280 nm. The liposoluble components were extracted by n-hexane and identified by gas chromatography-mass spectrometry （GC-MS）， and the contents of five fatty acids， namely palmitic acid， oleic acid， stearic acid， linolic acid and α-linolenic acid， were determined on a DB-35MS capillary column （0.25 mm×60.0 m， 0.25 µm）， the injection temperature was 250 ℃， the carrier gas was high-purity helium with a flow rate of 1.0 mL·min^-1 and the splitting ratio of 50∶1. The volatile oil was extracted by steam distillation method and its components were identified by GC-MS on a WM-5MS capillary column （0.25 mm×30.0 m， 0.25 µm） with the injection temperature of 250 ℃， the flow rate of 1.0 mL·min^-1 and the splitting ratio of 10∶1. ResultPrunellae Spica seeds were slightly smaller than chia seeds and basil seeds， and their color of seed coat was obviously different. Prunellae Spica seeds had strong water absorption and swelling characteristics， and the turgidity was 17.4 mL·g^-1， which was lower than that of chia seeds （25.2 mL·g^-1） and basil seeds （35.6 mL·g^-1）. Prunellae Spica seeds were rich in phenolic and fatty acids， while the content of volatile oil was very low. The main phenolic acids were salviaflaside and rosmarinic acid， with the contents of 0.579% and 0.392%， respectively. The total content of five fatty acids in n-hexane extract was 90.1%， and total content of unsaturated fatty acids was 80.6%， among which content of α-linolenic acid was 50.0%， which was slightly lower than 57.2% of chia seeds and similar to 50.0% of basil seeds. ConclusionPrunellae Spica seeds have good turgidity， rich in phenolic acids and unsaturated fatty acids， and especially with high amount of α-linolenic acid. It is worthy of being developed as functional food to realize comprehensive utilization of the waste resources of Prunellae Spica.

ObjectiveTo prepare matrine lipid-based cubic liquid crystalline nanoparticle （MAT-LLCN） gels and investigate its in vitro release and transdermal absorption behavior. MethodTaking entrapment efficiency as the index， the optimal formulation of MAT-LLCN was screened by extreme vertex mixture method based on the optimal ratio of glycerol monooleate （GMO） to poloxamer 407 （P407）， and its drug loading was investigated. MAT-LLCN gels was prepared by mixing MAT-LLCN with pre-swelled carbomer 940 as the gel matrix. The structure of MAT-lipid-based cubic liquid crystalline （LLC） was characterized by polarized light microscopy （PLM） and small angle X-ray scattering （SAXS）. The in vitro release and transdermal absorption properties of MAT-LLCN gels and MAT ordinary gels were compared by modified Franz diffusion cell method， skin structure changes caused by them were observed by hematoxylin-eosin （HE） staining. ResultThe optimal formulation of MAT-LLCN gels was 5.5% of GMO-P407 （9∶1）， 1%-6% of MAT， 0.6% of carbomer 940， adding water to sufficient amount. The prepared MAT-LLC was confirmed as body-centered （Im3m） LLC. The in vitro release behavior of MAT-LLCN gels was in accordance with the Weibull equation （R²=0.954 0）， and the release mechanism was the Fick diffusion. In vitro transdermal test showed that all the parameters of MAT-LLCN gels were higher than those of MAT ordinary gels （P<0.05）， including cumulative release rate， steady-state release rate and the amount of drug retention in skin. HE staining results showed that MAT-LLCN gels could loose the cellular arrangement of skin stratum corneum， and maintain the stability of the cell structure of the dermis. ConclusionThe prepared MAT-LLCN gels can accelerate the transdermal drug transport and form drug storage in the dermis by rapidly opening the skin stratum corneum barrier， suggesting that LLC has good application prospects in the field of transdermal drug delivery.

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

Objective:To identify gene mutations in a family with incontinentia pigmenti, in order to confirm pathogenic mutations.Methods:Clinical data were collected from all patients in a family with incontinentia pigmenti. DNA was extracted from peripheral blood samples obtained from the patients, healthy members in the family, and 100 unrelated healthy controls, and Sanger sequencing was performed for all exons and their flanking sequences of the NEMO gene.Results:Totally, there were 4 patients in the 4-generation family, who all presented with typical skin lesions and different symptoms. Genetic testing indicated that the proband and the other 3 patients all carried a heterozygous nonsense mutation c.1153C>T (p.Gln385X) at position 1153 in exon 8 of the NEMO gene, which led to the substitution of the glutamine codon (CAG) by the termination codon (TAG) at amino acid position 385. The mutation was not identified in the 14 healthy relatives or 100 unrelated healthy controls. The mutation cosegregated with incontinentia pigmenti in the family. Database searching confirmed the mutation to be a novel nonsense mutation, and it was considered as a very strong pathogenic locus according to the American College of Medical Genetic and Genomics guidelines.Conclusion:The mutation c.1153C>T in the NEMO gene is associated with the occurrence of incontinentia pigmenti in this family.