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 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.

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.

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 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.

【Objective】 To construct the eukaryotic expression vector carrying the human wild-type p27 and lacking nuclear localization signal p27△NLS coding sequences， and the express them in HEK293T cells， which may contribute to investigating the different locations and roles of p27 in the cytoplasm and nucleus. 【Methods】 Total RNA was prepared from human breast cancer MCF7 cells， and cDNA was obtained by reverse transcription-polymerase chain reaction （RT-PCR）. After amplification of the p27 CDs and non-NLS fragments by PCR， full length p27WT （CDKN1B， NM_004064.5） and p27△NLS coding regions were obtained. PCR products were then subcloned into the eukaryotic expression vector pCMV-Blank. After identification with bacterial PCR， double restriction enzyme digestion and sequencing， they were defined officially as pCMV-p27WT and pCMV-p27△NLS， respectively. The recombinant plasmids were transfected into HEK293T cells by electroporation. After 48 h， the levels of p27 protein in the cytoplasm and nucleus were detected by Western blotting. 【Results】 The sequencing results showed that the sequences of p27WT and p27△NLS inserted into the plasmids were both correctly consistent with that of NM_004064.5. After transfection with pCMV-p27WT， total p27 protein expression was increased and distributed in both the cytoplasm and nucleus of HEK293T cells. After transfection with pCMV-p27△NLS， p27 protein was significantly increased and almost entirely localized in the cytoplasm of HEK293T cells. 【Conclusion】 The eukaryotic expression plasmids of human p27WT and p27△NLS coding sequences were successfully constructed and overexpressed in HEK293T cells. This research may lay a foundation for investigating the biological function of p27 in the cell cycle progression of tumor cells.

Objective:To explore the characteristics of attention bias in patients with type D personality coronary heart disease (CHD), and provide a new theoretical perspective for elucidating the effect of type D personality on the pathogenesis of CHD and formulating prevention strategies.Methods:From March 2021 to September 2021, a total of 40 CHD patients who were hospitalized in the 2nd Affiliated Hospital of Harbin Medical University were enrolled using the convenient sampling method and event-related potential (ERP). Patients were divided into the type D personality group and the non-type D personality group by Type D Personality Scale-14, and matched according to age, gender and years of education. The Self-Rating Depression Scale was used to exclude patients with depression. The Negative Cognitive Processing Bias Questionnaire (NCPBQ) was used to measure negative cognitive processing bias. Dot-probe task and ERP technology were used to analyze the characteristics of attention bias, with the emotional face images as experimental stimulation materials.Results:A total of 15 CHD patients with type D personality and 15 CHD patients without type D personality were enrolled. The scores of NCPBQ and negative rumination bias dimension of CHD patients with type D personality were higher than those of CHD patients without type D personality, and the differences were statistically significant ( P<0.05). Behavioral experiments data showed that CHD patients without type D personality had a shorter response time to positive face images than negative face images in inconsistent conditional stimulation ( F=10.646, P<0.05), CHD patients without type D personality had a shorter response time to negative face images in consistent prompt type than inconsistent prompt type ( F=4.744, P<0.05). ERP experimental data showed that CHD patients with type D personality has higher N1 amplitude facing negative and positive face images stimulation ( F=8.973, P<0.05), CHD patients without type D personality had higher P3 amplitude facing positive face images stimulation ( F=6.750, P<0.05) . Conclusions:CHD patients with type D personality patients have negative cognitive processing bias, and they are more sensitive to emotional stimulation, invest more attention in the early stage of cognitive process, and have difficulty in disengaging attention from negative stimulation. Clinical medical staff should reduce negative stimulation and carry out positive psychological intervention in CHD patients with type D personality to reduce the adverse effects of negative stimulation on the prognosis of patients.

Objective:To observe central responses and functional connectivity (FC) during urinary bladder storage in neurogenic overactive bladder (NOAB).Methods:Twenty patients with NOAB were recruited. Resting state functional magnetic resonance imaging (rs-fMRI)were performed in all subjects under the following two conditions: empty bladder state and full bladder (strong desire to void)state. Software MATLAB, SPM8 and DPABI were adopted to analyze the difference of brain imaging between the two conditions. Voxel-based analysis of the REHO was performed to analyze rs-fMRI data including the main excitatory regions and inhibitory areas, peak value(X-axis, Y-axis, Z-axis), clusters size (active volume unit: number of voxel), T value(the excitatory and inhibitory extent of brain active regions). Voxel-based analysis of the REHO maps and FC between empty and full bladder were performed.Results:Increased activity during strong desire to void with NOAB patients was observed in the left orbital part of superior frontal, right middle frontal gyrus, and right superior frontal. Decreased activity was observed in right precentral. FC analysis found that these activated or deactivated brain regions were widely connected with other brain areas, include: frontal lobe, parietal lobe, temporal lobe, cingulate gyrus, lenticular nucleus, insular lobe, angular gyrus, parahippocampal gyrus and anterior and posterior central gyrus.Conclusions:Our results suggested that the right frontal robe may play a role in the control of bladder with NOAB during strong desire to void, and inhibitory areas located in right precentral. In NOAB patients, excitatory and inhibitory connections were increased in frontal lobe and central gyrus, decreased in insular lobe and parhippocampal gyrus.