Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hepatitis C in Henan province from 2012 to 2022.Methods:The case report data on hepatitis C from counties and districts in Henan between 2012 and 2022 were collected. The distribution characteristics were analyzed by descriptive epidemiological methods, and GeoDa1.2 software was used to perform spatial autocorrelation analysis. The spatiotemporal epidemiological analysis was conducted using SaTScan 10.1 software.Results:A total of 274 485 hepatitis C cases were reported in Henan from 2012 to 2022. The reported annual average incidence rate was 25.84/100 000 and showed an overall downward trend from 2012 to 2022 ( Z=-4.05, P<0.001). More cases were reported in women. The cases were mainly aged 40-69 years and farmers. Spatial autocorrelation analysis showed that the reported cases of hepatitis C present spatial clustering during 2012—2022, and the areas with high incidence were mainly distributed in counties or districts of Zhengzhou, Zhumadian, Xuchang, Zhoukou, and Nanyang. One class I clustering area was detected by spatiotemporal scanning, which mainly covered Xuchang, Pingdingshan and the surrounding counties ( LLR=16 117.73, RR=1.81, P<0.001). Conclusion:The reported cases of hepatitis C in Henan Province show an overall downward trend from 2012 to 2022 and present spatiotemporal clustering. The seasonal regularity of the hepatitis C epidemic is not obvious. People aged 40-69 years old and farmers are the key population for prevention and control.

Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.

In February 2025, a local cluster outbreak caused by the D8 genotype Measles virus (MV) was first discovered in Henan Province. Epidemiological investigations and laboratory testing were conducted, including the collection of serum and throat swabs for MV IgM antibody and nucleic acid detection, virus isolation and genetic homology analysis. Measures such as close contact tracing, vaccination rate assessment and supplementary immunization activities were implemented, successfully preventing broader community transmission. A total of three cases were reported during the outbreak, including one imported-related adolescent and two secondary local adult cases. All cases presented with typical symptoms such as fever and rash. Both adult cases were complicated by pneumonia, with one case developing into severe pneumonia. MV genotyping showed that the two secondary cases were both the D8 genotype, with the viral sequences being completely homologous to the Kazakhstan strain. Among the close contacts, 98.2% were adults, and 142 individuals received emergency vaccination.

Objective To compare the predictive effectiveness of the Glasgow coma scale(GCS),GCS-pupils scale(GCS-P),Glasgow-Pittsburgh coma scale(GPCS),full outline of unresponsiveness scale(FOUR),and coma recovery scale-revised(CRS-R)in forecasting the prognosis of severe stroke patients.Methods A prospective,consecutive cohort of severe stroke patients admitted to the Department of Neurology,First Medical Center of Chinese PLA General Hospital from September 2021 to April 2024 was enrolled.Demographic and clinical data were collected,including age,sex,length of hospital stay,diagnosis(severe ischemic stroke,severe cerebral hemorrhage,aneurysmal subarachnoid hemorrhage),medical history(hypertension,diabetes,coronary artery disease),smoking and drinking habits,vital signs upon admission(temperature,pulse,respiration,blood pressure),neurological examination findings(including speech and brainstem reflexes)at admission,head imaging results(CT,MRI)within 24 h of admission to assess the presence of brain herniation,and whether intubation occurred within 24 h of admission.Patients underwent GCS,GCS-P,GPCS,FOUR,and CRS-R scoring within 8h of admission.Telephone follow-up was conducted at 6 months post-stroke to assess outcomes using the modified Rankin scale(mRS),with mRS scores of 0-2 classified as the good prognosis group and 3-6 as the poor prognosis group.The receiver operating characteristic(ROC)curve was used to assess the prognostic prediction value of the five scales for poor outcomes at 6 months.The area under the ROC curve(AUC)was calculated,and pairwise comparisons of AUC were performed using the Delong test.Results A total of 179 severe stroke patients were enrolled,including 116 males and 63 females.The group consisted of 132 patients with severe ischemic stroke,30 with severe intracerebral hemorrhage,and 17 with aneurysmal subarachnoid hemorrhage.At 6months,126patients had a poor prognosis and 53 had a good prognosis.(1)There were statistically significant differences in age,temperature,pulse,history of coronary artery disease,smoking and drinking habits,presence of speech impairment,abnormal brainstem reflexes,brain herniation,intubation within 24 h of admission,and GCS,GCS-P,GPCS,FOUR,and CRS-R scores between the poor and good prognosis groups(all P＜0.05).(2)ROC analysis revealed that the AUC(95％CI)for predicting poor outcomes at 6 months in severe stroke patients for GCS,GCS-P,GPCS,FOUR,and CRS-R were 0.808(0.742-0.863),0.815(0.750-0.869),0.828(0.765-0.880),0.841(0.780-0.892),and 0.831(0.768-0.883),respectively.Sensitivities were 76.98％,78.57％,82.54％,84.13％,and 82.54％,and specificities were 73.58％,73.58％,67.92％,71.70％,and 73.58％,respectively.The FOUR had the highest AUC,with an optimal cutoff value of 13.(3)Pairwise comparisons of AUC showed a statistically significant difference between the FOUR and GCS(the difference value of AUC is 0.034,95％CI 0.004-0.064,Z=2.194,P=0.028),but no significant differences were observed between other scales(all P＞0.05).Conclusion Compared to GCS,GCS-P,GPCS,and CRS-R,FOUR may provide more valuable prognostic information for severe stroke patients.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.