Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1)checkpoint inhibitor combined with radiation therapy through whole-body dynamic 18 F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT)and Patlak multi-parametric analysis.Methods B16F10 mel-anoma dual-tumor mouse model was established and randomly divided into control,PD-1 monoclonal antibody,ra-diation-only,and combination groups(n=6).Whole-body 18F-FDG PET/CT imaging was performed before and 24 hours post-treatment.The changes of maximum standardized uptake value(SUVmax)and metabolic rate of FDG(MRFDG)changes were analyzed and compared.Mice were then euthanized,tumors excised and underwent histo-pathology with HE,CD8,Ki-67 staining to assess immune infiltration and proliferation.Distal tumor volumes were monitored during treatment.Results At 24 hours post-treatment,in the primary tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group(P＜0.000 1),while they decreased in the combination treatment group(P＜0.000 1),with statistically significant differences.In the distal tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group,PD-1 monoclonal antibody group,and radiothera-py-alone group.The SUVmax differences were statistically significant in the control group before and after treatment(P＜0.000 1).MRFDG values in the distal tumors showed statistically significant differences in all three groups(P＜0.01 or P＜0.000 1).In the combination treatment group,SUVmax and MRFDG values in the distal tumors de-creased significantly compared to pre-treatment(P＜0.000 1).Post-treatment comparison of SUVmax and MRFDG values in the distal tumors showed that statistically significant differences in SUVmax and MRFDG values were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(all P＜0.05).Im-munohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P＜0.001);the mean absorbance value of Ki-67 immuno-histochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P＜0.001).Conclusion The synergistic effects of combined treatment reduced distal tumor growth.Whole-body 18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma,providing reliable imaging parameters for optimizing combinatorial therapies.

Objective To prepare T cell immunoglobulin domain and mucin domain 1 protein-1(TIM-1)-Fc fusion protein,and to investigate the intervention effect of TIM-1-FC fusion protein on ovabumin(OVA)-induced asthma mice as well as its po-tential mechanism.Methods Through genetic engineering,pcDNA3.1(+)-TIM-1-Fc plasmid was constructed and stably transfected into CHO cells.Cell culture supernatant was collected and purified,and TIM-1-Fc fusion protein was ob-tained.Mouse model of allergic asthma was established by intraperitoneal injection of OVA aluminum hydroxide solution.The mice were randomly divided into control group,asthma group and TIM-1-Fc intervention group.The TIM-1-Fc intervention group included TIM-1-Fc nasal drop group and TIM-1-Fc injection group.20 min before each intervention,40 μL ovalbumin sa-line solution(OVA-NS)was used for nasal drops.Protein TIM-1-Fc nasal drops group(1 μg/40 μL TIM-1-Fc nasal drops was administrated in each mouse)and TIM-1-Fc injection group(6 μg/200 μL TIM-1-Fc was injected intraperitoneally in each mouse)were interfered with TIM-1-Fc fusion,once a day for 7 days.Normal saline was used as replacement in the control group.Hematoxylin-eosin staining(HE)was used to observe the pathological changes of lung tissue.Flow cytometry was used to detect the proportion of type 2 helper T cells(Th2),type 17 helper T cells(Th17),regulatory T cells(Treg)and the levels of related cytokines in peripheral blood of mice.Results TIM-1-Fc fusion protein and OVA-induced allergic asthma mouse model was successfully constructed.Compared with asthma group,TIM-1-Fc fusion protein could significantly reduce airway inflam-matory injury and lung tissue injury in asthmatic mice.TIM-1-Fc fusion protein intervention could significantly reduce the pro-portion of TIM-1 CD4+T cells and TIM-1+Th17 cells in peripheral blood,increase the number of TIM-1+Treg cells,signifi-cantly reduce the proportion of Th2 and Th17 cells,and increase the proportion of Treg cells.It could modulate Th1/Th2 and Th17/Treg immune imbalances in asthma.Conclusion TIM-1-Fc fusion protein improves airway inflammation and lung tissue injury in OVA-induced allergic asthma mice,and its mechanism may be related to the immune regulation of Th1/Th2 and Th17/Treg by TIM-1-Fc fusion protein.

Objective:To explore the symptom management experience in young and middle-aged patients with home peritoneal dialysis.Methods:Using the descriptive phenomenological research method and purposive sampling method, 13 young and middle-aged peritoneal dialysis patients were selected for semi-structured interviews, and the interview data was analyzed and sorted out to extract themes.Results:A total of four themes were summarized, including difficulties in symptom management (lack of symptom management knowledge, insufficient symptom perception ability), effect of poor symptom management effectiveness (limited daily life behavior, weakened family roles, obstacles in returning to the workplace, withdrawal of social activities and increased economic burden), polarized symptom management coping strategies (positive and negative responses) and multifaceted symptom management needs (longing for new treatment methods, hoping for disease knowledge popularization and craving for social support in various aspects) .Conclusions:There are many obstacles and needs in the process of symptom self-management of young and middle-aged home peritoneal dialysis patients. It is suggested that medical staff should combine the characteristics and psychology of middle-aged and young peritoneal dialysis patients, implement targeted intervention measures, and improve their symptom management ability.

Objective To explore the effect of traditional Chinese medicine enema combined with acupoint massage on postoperative intestinal function recovery.Methods A total of 80 patients with abdominal surgery admitted to First Affiliated Hospital of Huzhou University from January 2022 to June 2023 were selected and divided into study group and control group according to random number table method,with 40 cases in each group.The control group was treated with conventional Western medicine,while the study group was treated with traditional Chinese medicine enema combined with acupoint massage on the basis of conventional Western medicine treatment.The therapeutic effect,postoperative recovery time,gastrointestinal hormone level,abdominal distension pain and gastrointestinal reaction score were compared between two groups.Results Postoperative bowel sound recovery time,first anal defecation time and full-flow diet recovery time in study group were significantly shorter than those in control group(P<0.05).At 5 days after surgery,the levels of motilin(MTL),gastrin(GAS)and gastric inhibitory peptide(GIP)in two groups were significantly higher than those in this group at 1 day after surgery(P<0.05).The levels of MTL,GAS and GIP in study group were significantly higher than those in control group(P<0.05).At 5 days after surgery,abdominal distension score and gastrointestinal reaction score in two groups were significantly lower than those in this group 1 day after surgery(P<0.05),and abdominal distension score and gastrointestinal reaction score in study group were significantly lower than those in control group(P<0.05).The total effective rate of study group was significantly higher than that of control group(χ2=3.914,P=0.048).Conclusion Traditional Chinese medicine enema combined with acupoint massage can effectively shorten the recovery time of intestinal function,improve the level of gastrointestinal hormone,relieve abdominal distension pain and gastrointestinal reaction after abdominal operation,and the effect is significant,worthy of clinical application.

Objective : To investigate the trends in incidence of malignant tumors in Yongkang City, Zhejiang Province from 2013 to 2019, so as to provide insights into formulation of the malignant tumor control strategy. Methods: Data pertaining to the incidence of malignant tumors from 2013 to 2019 were captured from the Zhejiang Chronic Disease Monitoring Information System. Based on the International Classification of Diseases 10th Revision (ICD-10) and data from the national population census, the constituent ratio, crude incidence and Chinese population-standardized incidence of malignant tumors were estimated, and the trends in incidence of malignant tumors were investigated using annual percent change (APC). Results: The annual mean crude incidence and Chinese population-standardized incidence of malignant tumors were 356.75/105 and 226.97/105, which both appeared an overall tendency towards a rise (APC=5.887% and 4.815%, both P<0.05). The crude incidence of malignant tumors appeared a tendency towards a rise among both men (APC=3.860%, P<0.05) and women (APC=8.534%, P<0.05) from 2013 to 2019, and the Chinese population-standardized incidence of malignant tumors appeared a tendency towards a rise among women (APC=8.392%, P<0.05). The largest increase in the crude incidence of malignant tumors was seen among women at ages of 15 to 44 years (APC=11.599%, P<0.05). In addition, the Chinese population-standardized incidence of lung cancer, colorectal cancer and thyroid cancer all showed a tendency towards a rise among men (all P<0.05), and the Chinese population-standardized incidence of lung cancer and thyroid cancer both appeared a tendency towards a rise among women (both P<0.05). Conclusions The incidence of malignant tumors showed a tendency towards a rise in Yongkang City from 2013 to 2019, and the elderly and young females are high-risk populations for malignant tumors. Lung cancer, thyroid cancer and colorectal cancer are cancers that should be given a high priority.

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

Objective:To investigate the effect of using two different input functions to reconstruct 18F-FDG PET/CT Patlak multi-parameter images on the quantitative parameters of lung cancer lesions. Methods:The original whole-body dynamic 18F-FDG PET/CT scan data of lung cancer patients in the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University were retrospectively analyzed. The total scan time was 75 min. Two input functions were used for Patlak multi-parameter reconstruction: ① Image-derived input function(IDIF)using the Time-activity curve(TAC)of descending aorta from 0 min to 75 min. ② Population-based input function (PBIF) developed by Yale University. Metabolic rate of FDG (MR FDG) and Distribution volume (DV) images were obtained by Patlak multi-parameter analysis software using the above input functions. The region of interest (ROI) method was used to delineate the lesions to obtain multi-parameter quantitative information, including the max, peak and mean value of MR FDG and DV. Paired t-test was used for statistical analysis. Results:The original data of 27 lung cancer patients who received whole-body dynamic 18F-FDG PET/CT imaging were reconstructed by Patlak with two different input functions. The max, peak and mean values of MR FDG-IDIF and MR FDG-PBIF in lung cancer lesions were as follows: (0.26 ± 0.15), (0.19 ± 0.12), (0.14 ± 0.08)μmol·min -1·ml -1 and (0.26 ± 0.15), ( 0.20 ± 0.13), (0.15 ± 0.09)μmol·min -1·ml -1, with no statistically significant difference between two functions( P > 0.05). The max, peak and mean values of DV IDIF and DV PBIF were (165.56 ± 99.89)%, (117.66 ± 72.24)%, (62.16 ± 33.65)% and(170.04 ± 103.93)%, (121.91 ± 73.71)%, (65.05 ± 37.17)%, with no statistically significant difference between two functions ( P > 0.05). Conclusions:The population-based input function may be an alternative for patients who could not lie supine for long time during whole-body dynamic 18F-FDG PET/CT Patlak multi-parameter imaging.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To explore the application effect of new whole-course closed sputum specimen collection technology in intensive care unit patients.Methods:From April 2020 to January 2022, the convenient sampling was used to select 442 ICU mechanical ventilation patients admitted to 6 hospitals in Jiaxing City as the research objects. According to the order of admission time, the patients were divided into the control group ( n=221) and the experimental group ( n=221) . The control group adopted the traditional open sputum specimen collection technology, while the experimental group adopted the new whole-course closed sputum specimen collection technology. The heart rate, the incidence of hypooxygen saturation and the incidence of sputum spatter were compared between the two groups after sputum sample sampling. Results:The incidences of hypooxygen saturation and sputum spatter in the experimental group were lower than those in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The new whole-course closed sputum specimen collection technology can effectively stabilize the oxygen saturation of ICU patients in the process of sputum specimen collection, reduce the incidence of sputum spatter and promote the safety of both patients and medical staff, which is worthy of clinical promotion and application.

Objective:To explore the effect of “trinity”co-management mode in prevention of venous thromboembolism（VTE）during perioperative period in patients undergone major orthopedic surgery.Methods:A retrospective case-control study was conducted to analyze the clinical data of 120 patients undergone major orthopedic surgery in Second Affiliated Hospital of Wenzhou Medical University from January 2019 to August 2019，including 46 males and 74 females at age range of 43-89 years［（63.7 ±11.3）years］. Of all，58 patients were with intertrochanteric fracture，52 with femoral neck fracture and 10 with gonarthrosis. Hip fracture operation was performed in 58 patients，total hip replacement in 37，artificial femoral head replacement in 15 and total knee replacement in 10. A total of 60 patients were treated with traditional care，including traditional prevention of thrombosis，conventional VTE risk assessment，treatment and related health education（traditional care group），and 60 patients a with “trinity” co-management care（co-management care group）on the basis of the traditional care，including the trinity of health education，establishing VTE prevention group and VTE tracking table，strengthening postoperative rehabilitation care and exercise，optimization of medicine，nutrition and pain management. Swelling rate of injured limb，D-dimer level on admission and at postoperative days 3 and 7，incidence of VTE at postoperative day 7，length of hospital stay and patient satisfaction were compared between the two groups.Results:Three days and seven days after operation，swelling rate of the injured limb in co-management care group［13%（8/60），8%（5/60）］was significantly lower than that in traditional care group［42%（25/60），30%（18/60）］（ P < 0.05）. There was no significant difference in level of D-dimer between the two groups on admission（ P > 0.05）. Three days and seven days after operation，level of D-dimer［3.40（2.11，6.10）μg/ml，3.70（2.61，6.82）μg/ml］in co-management care group was significantly lower than that in traditional care group［6.37（3.60，9.81）μg/ml，6.42（3.62，9.83）μg/ml］（ P < 0.01）. Seven days after operation，incidence of VTE in co-management care group［3%（2/60）］was significantly lower than that in traditional care group［13%（8/60）］（ P < 0.05）. Length of hospital stay in co-management care group［（10.1 ± 2.2）days］was shorter than that in traditional care group［（11.4 ± 4.3）days］（ P < 0.05）. Nursing satisfaction was 93%（56/60）in co-management care group，higher than 72%（43/69）in traditional care group（ P < 0.05）. Conclusion:For patients undergone major orthopedic surgery，“trinity” co-management mode is effective to reduce the incidence of postoperative limb swelling，level of D-dimer as well as incidence of VTE，shorten the length of hospital stay and improve patients’ satisfaction during perioperative period.