Objective To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics(RG)technology,in combination with chemotherapy drug,gemcitabine(GEM),against pancreatic cancer cells.Methods The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study.The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay.CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses[multiplicities of infection(MOI):0,0.1,1.0,3.0]on the survival rate of pancreatic cancer cell lines(Panc02,PANC-1,SW1990,BxPC-3)and normal pancreatic ductal epithelial cells(HPDE6-C7)after treatment for 24,48 or 72 h.Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice(6 weeks old)were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group.PBS(100 μL/animal)or OvFlu-GM-CSF virus(1× 107PFU/100 μL)was given to the mice of the corresponding groups through intratumoral injection,while GEM(100 mg/kg)was injected intraperitoneally,once per 3 days,for totally 9 times.Changes in tumor volume and survival rate were monitored.Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues.HE staining was performed to observe the pathological changes in major organs(heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured to evaluate the safety of the recombinant oncolytic virus.Results The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells.At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0(P＜0.01).The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time(P＜0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells(HPDE6-C7).In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment(P＜0.01),and enhanced the infiltration of T cells in the tumor tissues.No obvious pathological changes were observed in the above-mentioned major organs.Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.Conclusion RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host's anti-tumor immune response.

Objective To investigate the therapeutic effect of combination treatment of transcatheter arterial chemoembolization(TACE),micro wave ablation(MW A)and targeted immunotherapy for hepatocellular carcinoma(HCC).Methods The clinical data of HCC patients,who were admitted to the Affiliated Central Hospital of Jiangnan University of China to receive TACE from August 2016 to August 2023,were retrospectively analyzed.Based on the inclusion criteria,a total of 252 patients were included in this study.According to the therapeutic scheme,the patients were divided into combination group(receiving TACE,MWA,targeted therapy and immunotherapy,n=41),and control group(receiving TACE alone,n=211).The overall survival(OS)and progression-free survival(PFS)of the two groups were statistically analyzed.After propensity score matching at 1∶1 ratio,the clinical effects of the two groups were analyzed.According to different data,t-test,test,Kaplan-Meier curve,logarithmic rank test,Cox regression analysis,or Cox proportional risk model analysis was used to make statistical analysis.Results Multivariate regression analysis showed that tumor number,maximum diameter,invasion of large vessels,tumor capsule,AFP level,glutamic oxalacetic transaminase,BCLC stage and Child-Pugh stage were the independent risk factors for patient survival.Imaging response and combination treatment were the protective factors for survival.After propensity score matching,a total of 37 pairs of patients were obtained,and the baseline data were comparable between the groups.The differences in OS and PFS between the two groups were statistically significant.Combination treatment of TACE,MWA,targeted therapy and immunotherapy could significantly prolong OS and PFS in HCC patients.Conclusion Compared with TACE alone,combination use of TACE,MWA,targeted therapy and immunotherapy is a more effective therapeutic scheme for HCC,it can remarkably and effectively improve OS and PFS in HCC patients.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective To investigate the geographical distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Henan Province in 2023, so as to provide insights into the prevention and control of visceral leishmaniasis vectors. Methods A total of 23 counties (districts) were sampled from 18 cities of Henan Province from May to September, 2023 as sandfly surveillance sites, and sandflies were captured using human capture and light trapping methods. Following morphological identification, the changes in the sandfly density were calculated at different months and in different breeding habitats. Results A total of 406 light traps were set at sandfly surveillance sites in Henan Province from May to September, 2023, and a total of 3 137 female sandlies were captured, with an average density of 7.73 sandlies/(light·night). A total of 1 494 Phlebotomus chinensis sandflies were captured, including 1 222 female sandflies, with an average density of 3.01 sandflies/(light·night), and the highest density of P. chinensis was found in Gongyi City [17.00 sandflies/(light·night)]. A total of 5 544 sandflies were captured using the human capture method, including 230 P. chinensis, and the density of P. chinensis appeared a unimodal distribution, with a peak in early July [5.81 sandflies/(light·night)]. Among different breeding habitats, the highest P. chinensis density was detected in pigpens [4.50 sandflies/(light·night)]. Conclusions P. chinensis was predominantly distributed in hilly areas of northern and central-western Henan Province in 2023, and the sandfly density appeared a unimodal distribution. Intensified monitoring of visceral leishmaniasis vectors is recommended.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative acute kidney injury (AKI) in elderly patients undergoing long-time abdominal surgery.Methods:The medical records from elderly patients of both sexes, aged ≥ 65 yr, with a duration of operation ≥ 8 h and American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective first abdominal surgery for gastrointestinal tumors at the Shanxi Provincial People′s Hospital from October 1, 2016 to June 30, 2022, were collected from the electronic medical record database. Patients were divided into conventional fluid therapy group (group C) and GDFT group (group G) according to whether GDFT was employed during operation. In group C, blood pressure was maintained ≥90/60 mmHg or mean arterial pressure≥65 mmHg, and urine output more than 30 ml/h. In group G, the stroke volume variation was maintained ≤13%, and cardiac index ≥2.5 L·min -1·m -2. The patient general characteristics, requirement for fluid, urine output, blood loss, requirement for vasoactive agents and abdominal hyperthermic perfusion, and operation time were recorded during operation. The development of AKI within 72 h after operation and development of other complications (pneumonia, anastomotic leakage, surgical site infection, septic shock, arrhythmia) after operation were recorded. The length of hospital stay and 30-day mortality after operation were recorded. Results:A total of 125 patients were included in this study, with 41 patients in group C and 84 patients in group G. Postoperative AKI occurred in 19 patients, with an incidence of 15.2%. Compared with group C, the requirement for colloid, total volume of fluid infused and urine volume were significantly decreased during operation, the requirement for vasoactive agents was increased during operation ( P<0.05), the risk of postoperative AKI was reduced ( OR=0.23, P<0.05), and no significant change was found in the incidence of other postoperative complications, 30-day mortality, and length of hospital stay in group G ( P>0.05). Conclusions:GDFT can reduce the risk of AKI in the elderly patients undergoing long-time abdominal surgery.

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghre-lin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMHCART neurons was evalua-ted.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic pa-raventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,periph-eral injection of ghrelin significantly increased the expression of DMHC ART immunoreactive neurons(P=0.037 3).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.004 0)and feed intake(P=0.023 1).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.

Vesicular glutamate transporter 2(VGlut2)is expressed in the PVN of the hypothalamic paraventricular nucleus(PVNVG1ut2)as an excitatory neurotransmitter,which regulates food intake and energy metabolism and plays an important role in maintaining homeostasis.However,it is not clear that the upstream and downstream projection network of PVNVGut2 neurons hinders the anal-ysis of glutamatergic neuron circuit function.Anterograde and retrograde tracer viruses were injec-ted into the PVN of VGlut2 mice by stereotactic brain injection technique to find the input and output nuclei of PVNVGlut2 neurons.Anterograde tracing results showed that PVNVGlut2 neurons pro-jected to the downstream medial amygdala(MeAD)and arcuate nucleus(ARC).Retrograde trac-ing results showed that PVNVGlut2 received input from the prefrontal nucleus(Pr),the reticular tegmental nucleus(RtTg),and the hypoglossal nucleus(12N).In addition,VGlut2 was found to be co-expressed with neuronal nitric oxide synthase(nNOS)neurons in the PVN.The anatomical net-work of PVNVG1ut2 neurons was analyzed by virus tracking tool,which laid the anatomical founda-tion for further study on the functional regulation of PVNVGlut2.

Humans ; Asthma/drug therapy* ; Biological Therapy