ObjectiveTo analyze the epidemiological and clinical characteristics of pertussis in Taizhou City, Zhejiang Province, 2024, and to provide a scientific basis for formulating local prevention and control strategies. MethodsCase data and population data were obtained from the China Disease Prevention and Control Information System. Epidemiological case investigation data were collected from the Zhejiang Vaccine Clinical Research and Application Effectiveness Evaluation System and the Immunization Service Information System. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distributions, and SaTScan 9.7 software was applied for spatiotemporal cluster scanning. ResultsIn 2024, a total of 3 090 pertussis cases were reported in Taizhou City, with no deaths. The number of reported cases increased significantly compared with those in previous years, and the peak occurred in April. Spatiotemporal scanning identified three clusters: a most likely cluster centered around Tantou Town in Tiantai County, covering 16 streets/towns, a second most likely cluster centered around Taiping Subdistrict in Wenling City, covering 11 streets/towns, and a third most likely cluster centered around Ganjiang Town in Yuhuan City, covering 6 streets/towns. The three clusters together accounted for 31.04% of the total scanned cases.The majority of cases were in the 6‒10 years age group (55.02%), and students accounted for the highest proportion by occupation (44.17%). Among 2 929 epidemiological investigation cases, the most common clinical manifestations were cough (97.58%) and aggravated nocturnal cough (52.10%), while typical symptoms (including paroxysmal spasmodic cough and post-tussive vomiting, etc.) were less frequent. Among the cases, 82.49% had completed the full 4-dose vaccination schedule, and their complication rate (10.47%) was lower than that of the unvaccinated group (20.56%). ConclusionThe number of reported pertussis cases surged in Taizhou City in 2024, showing significant spatiotemporal clustering, with school‑aged children being the high‑risk group. Vaccination could reduce the risk of complications. It is recommended to further enhance surveillance sensitivity, with a focus on strengthening immunization strategies for high-risk groups such as school-aged children aged 6‒10 years, and to reinforce targeted protection for infants under 1 year old who have not completed primary vaccination, along with their families. In addition, prevention and control resources should be deployed in advance for the cluster areas identified through spatiotemporal analysis and for the spring peak season,to interrupt local transmission chains.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

ObjectiveTo investigate the effects of partial hepatic ischemia/reperfusion (I/R) on choline acetyltransferase(ChAT) expression in hippocampal neuron in mice.MethodsOne hundred adult male mice,aged 2 months,weighing 20-25 g,were randomly divided into 5 groups (n =20 each): normal control group(group C),sham operation group(group S),groups I/R1,I/R2,I/R3.Partial hepatic ischemia was produced by clamping left hepatic artery and portal vein for 20,30,40 min respectively followed by reperfusion in groups I/R1,I/R2,I/R3.Passive avoidance task was performed with 10 mice in each group at 4-9 and 18-23 d after operation respectively.The animals were sacrificed and their brains were removed for determination of the expression of ChAT in CA3 of hippocampal neuron.ResultsCompared with group C,the latency was significantly shortened and number of errors increased in groups I/R1 and I/R2 at 4-7 d after operation and in group I/R3 at 4-9 d after operation,the expression of ChAT in hippocampal neuron down-regulated in groups I/R1,I/R2 and I/R3 at 9 d after operation( P ＜0.05 or 0.01).There was no significant difference in the latency and number of errors at 18-23 d after operation and the expression of ChAT in hippocampal neuron at 23 d after operation among groups C,I/R1,I/R2 and I/R3 ( P ＞ 0.05).Compared with group I/R1,the number of errors was significantly increased at 4 and 5 d after operation in group I/R2,the latency shortened at 4-6 d after operation and number of errors increased at 4-9 d after operation in group I/R3,and the expression of ChAT in hippocampal neuron down-regulated at 9 d after operation in groups I/R2 and I/R3 ( P ＜ 0.05 or 0.01 ).There was no significant difference in the latency and number of errors at 18-23 d after operation and the expresson of ChAT in hippocampal neuron at 23 d after operation among groups I/R1,I/R2 and I/R3 ( P ＞ 0.05).ConclusionPartial hepatic I/R can result in transient cognitive impairment in mice by down-regulating the expression of ChAT in hippocampal neuron.

Objective Exogenous small-diameter vascular grafts have been developed with tissue-engineered small-di-ameter vascular grafts for the reconstructive surgery in the treatment of patients with coronary artery diseases in whom restenosis of the initially transplanted autografts occurred.This study was conducted to develop decellularized umbilical arteries (HUAs) and evaluate their physical and mechanical properties,as well as to assess the usefulness of decellularized HUAs in the coronary artery bypass grafting procedures.Methods After HUAs were harvested,their inner diameters were measured with a sliding caliper and the blasting pressure was measured with a pressure gauge.HUAs were firstly infused with a compound liquid consisted of 0.25％ Trypsin and 0.01％ Ethylene Diamine tetraacetic Acid(EDTA) and then with 1％ Sodium Lauryal Sulfate (SDS).Fragments of the vessels were collected and observed under light microscope and electron microscope.The mechanical characteristics of HUAs were identified with an electronic experiment machine before and after decellularization.Fibroblasts and endothelial progenitor cells growing along the lining of decelluarized human umbilical arteries(dHUAs) could be observed.Results The average inner diameter of HUAs was ( 3.50 ± 0.55 ) mm.Two of thirty HUAs were broken at a pressure of 300 mm Hg.The process for the lining of HUAs to be decellularized with a peristaltic pump took 0.5 hour with 0.25％ Trypsin and 0.01％ EDTA and 3 hours with 1％ SDS.Observations with light microscope and electron microscope demonstrated that all of the original lining cells were decellularized.The ultimate stress of the HUAs did not change significantly after decellularization ( P ＞0.05 ).Attached fibroblasts and endothelial progenitor cells could be seen along the decellular lining of the grafts and the ultimate stress of the HUAs did not change significantly after implantation of the two kinds of cells.Conclusion dHUAs,with good histocompatibility and properties mentioned above,may be used as potential vascular grafts in CABG.