Objective:To investigate the combined therapeutic role of the AKT inhibitor MK2206 and Ruxolitinib in treating Myeloproliferative Neoplasms (MPN) driven by a calreticulin (CALR) gene mutation.Methods:① Murine bone marrow c-kit + cells were isolated by sacrificing mice and harvesting bone marrow from the femur, tibia, and ilium for subsequent c-kit + cell sorting. ② A CALR transplantation mouse model was established. GFP-tagged retroviral vectors containing either the CALR gene mutation or the migR1 control were constructed, packaged in Platinum-E cells, and used to transduce murine bone marrow c-kit + cells. These transduced cells were then transplanted into lethally irradiated female recipient mice via tail vein injection. ③ Following successful engraftment, the mice were randomly assigned to four treatment groups for intragastric administration. Complete blood counts were monitored periodically, and the spleen size and weight of transplanted mice were measured. ④ Flow cytometry was used to quantify the proportions of GFP + tumor cells, megakaryocytic lineage cells, and hematopoietic stem cells in both splenic and bone marrow tissues. Histopathological examination was performed to evaluate the degree of tumor cell infiltration in these organs. Results:① Following gavage treatment, peripheral blood platelet (PLT) and white blood cell counts were significantly lower in the combined AKT inhibitor MK2206 and Ruxolitinib group compared to the MK2206, Ruxolitinib, and control groups ( P<0.05). ② In comparison with the MK2206 and Ruxolitinib monotherapy groups, the combination therapy group exhibited a significant reduction in spleen weight and a marked improvement in splenomegaly at 30 weeks post-transplantation ( P<0.05). ③ After four weeks of continuous treatment, combined administration resulted in a significant decrease in the proportion of megakaryocytic lineage cells and GFP + tumor cells in the bone marrow and spleen ( P<0.05). Additionally, the proportion of hematopoietic stem cells in the bone marrow was also significantly reduced ( P<0.05). ④ Histopathological analysis (H&E staining) of bone marrow and spleen tissues confirmed that the combined regimen decreased both tumor cell infiltration and the proportion of abnormal megakaryocytes in these organs. Conclusion:The combination of AKT inhibitor MK2206 and Ruxolitinib is effective at significantly ameliorating disease symptoms and reducing tumor infiltration in vivo in mice with a myeloproliferative tumor transplantation driven by a CALR gene mutation.

Objective To observe the value of deep progressive reconstruction(DPR)algorithm for reconstructing whole-body 18 F-FDG PET images.Methods Totally 67 patients who underwent whole-body 18 F-FDG PET/CT were retrospectively enrolled.PET data of 30 s,60 s,90 s and 120 s per bed in equipment list were reconstructed using ordered subset expectation maximization(OSEM)and DPR algorithms,respectively.Finally 7 groups of reconstructed images were obtained,including OSEM_30,OSEM_60 and OSEM_120,also DPR_30,DPR_60,DPR_90 and DPR_120 groups.The subjective scores,also objective evaluation indexes,i.e.the maximum and mean standard uptake values(SUV)of lesions and livers,namely SUVmax and SUVmean,were compared,and target-to-background ratio(TBR),signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and coefficient of liver variation(CVliver)were calculated.Taken results based in OSEM_120 group as references,Bland-Altman plot was drawn to explore the consistency of SUV of lesions and livers obtained based on DPR_30,DPR_60 and DPR_90 groups with those in OSEM_120 group.Results Under the same acquisition time,subjective scores,SUVmax and SUVmean of lesions,TBR,SNR,CNR and CVliver in DPR_30,DPR_60 and DPR_120 groups were superior to those in corresponding OSEM_30,OSEM_60 and OSEM_120 groups(all P＜0.001).Compared with OSEM_120 group,subjective scores and SNR decreased but TBR and CVliver increased in DPR_30 group,while subjective and objective evaluation results in DPR_60 group and DPR_90 group increased(all P＜0.05)or being not significantly different from those in OSEM_120 group(all P＞0.05).No significant difference of liver SUV mean was found among 7 groups(P=0.955).SUVmax and SUVmean of lesions and livers obtained based on DPR_30,DPR_60 and DPR_90 groups were in good agreement with those oibtained based on OSEM_120 group.Conclusion Using DPR algorithm to reconstruct whole-body 18 F-FDG PET image could shorten acquisition time under the premise of ensuring image quality.

Objective To observe the value of deep progressive reconstruction(DPR)algorithm for reconstructing whole-body 18 F-FDG PET images.Methods Totally 67 patients who underwent whole-body 18 F-FDG PET/CT were retrospectively enrolled.PET data of 30 s,60 s,90 s and 120 s per bed in equipment list were reconstructed using ordered subset expectation maximization(OSEM)and DPR algorithms,respectively.Finally 7 groups of reconstructed images were obtained,including OSEM_30,OSEM_60 and OSEM_120,also DPR_30,DPR_60,DPR_90 and DPR_120 groups.The subjective scores,also objective evaluation indexes,i.e.the maximum and mean standard uptake values(SUV)of lesions and livers,namely SUVmax and SUVmean,were compared,and target-to-background ratio(TBR),signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and coefficient of liver variation(CVliver)were calculated.Taken results based in OSEM_120 group as references,Bland-Altman plot was drawn to explore the consistency of SUV of lesions and livers obtained based on DPR_30,DPR_60 and DPR_90 groups with those in OSEM_120 group.Results Under the same acquisition time,subjective scores,SUVmax and SUVmean of lesions,TBR,SNR,CNR and CVliver in DPR_30,DPR_60 and DPR_120 groups were superior to those in corresponding OSEM_30,OSEM_60 and OSEM_120 groups(all P＜0.001).Compared with OSEM_120 group,subjective scores and SNR decreased but TBR and CVliver increased in DPR_30 group,while subjective and objective evaluation results in DPR_60 group and DPR_90 group increased(all P＜0.05)or being not significantly different from those in OSEM_120 group(all P＞0.05).No significant difference of liver SUV mean was found among 7 groups(P=0.955).SUVmax and SUVmean of lesions and livers obtained based on DPR_30,DPR_60 and DPR_90 groups were in good agreement with those oibtained based on OSEM_120 group.Conclusion Using DPR algorithm to reconstruct whole-body 18 F-FDG PET image could shorten acquisition time under the premise of ensuring image quality.

Objective:To investigate the combined therapeutic role of the AKT inhibitor MK2206 and Ruxolitinib in treating Myeloproliferative Neoplasms (MPN) driven by a calreticulin (CALR) gene mutation.Methods:① Murine bone marrow c-kit + cells were isolated by sacrificing mice and harvesting bone marrow from the femur, tibia, and ilium for subsequent c-kit + cell sorting. ② A CALR transplantation mouse model was established. GFP-tagged retroviral vectors containing either the CALR gene mutation or the migR1 control were constructed, packaged in Platinum-E cells, and used to transduce murine bone marrow c-kit + cells. These transduced cells were then transplanted into lethally irradiated female recipient mice via tail vein injection. ③ Following successful engraftment, the mice were randomly assigned to four treatment groups for intragastric administration. Complete blood counts were monitored periodically, and the spleen size and weight of transplanted mice were measured. ④ Flow cytometry was used to quantify the proportions of GFP + tumor cells, megakaryocytic lineage cells, and hematopoietic stem cells in both splenic and bone marrow tissues. Histopathological examination was performed to evaluate the degree of tumor cell infiltration in these organs. Results:① Following gavage treatment, peripheral blood platelet (PLT) and white blood cell counts were significantly lower in the combined AKT inhibitor MK2206 and Ruxolitinib group compared to the MK2206, Ruxolitinib, and control groups ( P<0.05). ② In comparison with the MK2206 and Ruxolitinib monotherapy groups, the combination therapy group exhibited a significant reduction in spleen weight and a marked improvement in splenomegaly at 30 weeks post-transplantation ( P<0.05). ③ After four weeks of continuous treatment, combined administration resulted in a significant decrease in the proportion of megakaryocytic lineage cells and GFP + tumor cells in the bone marrow and spleen ( P<0.05). Additionally, the proportion of hematopoietic stem cells in the bone marrow was also significantly reduced ( P<0.05). ④ Histopathological analysis (H&E staining) of bone marrow and spleen tissues confirmed that the combined regimen decreased both tumor cell infiltration and the proportion of abnormal megakaryocytes in these organs. Conclusion:The combination of AKT inhibitor MK2206 and Ruxolitinib is effective at significantly ameliorating disease symptoms and reducing tumor infiltration in vivo in mice with a myeloproliferative tumor transplantation driven by a CALR gene mutation.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

The policy system for the construction and management of public hospital with multiple districts is gradually being established and improved,the game among stakeholders affects the effect of policy implementation.There are differences in the strictness of policy implementation on national and local health commission,deviations between local government urban development requirements and the hospital's own construction goals in the process of policy implementation.Based on the game theory of public policy implementation,it analyzes the influencing factors of one hospital with multiple districts and the focus issues encountered in policy implementation,put forward management suggestions for health commission and public hospitals.

Objective:To analyze the clinical advantages of the modified Trocar approach in laparoscopic cholecystectomy (LC) compared to the conventional three-hole approach.Methods:Clinical data of 202 patients undergoing the modified Trocar approach LC (the modified group) at the First Affiliated Hospital of Wenzhou Medical University from January 2015 to September 2023 were retrospectively analyzed, including 84 males and 118 females patients, aged (49.58±13.03) years old. The conventional group enrolled 606 patients, including 245 males and 361 females, aged (50.99±12.55) years old. The operative time, conversion to four-hole approach, postoperative complications, hospital stay, pain score, and satisfaction score were compared between the groups.Results:No severe complications occurred in either group. In modified group, three cases (1.5%, 3/202) required conversion to four-hole approach, while in conventional group, seven (1.2%, 7/606) required conversion, with one case conversed to open surgery ( P>0.05). The operative time in modified and conventional groups were (40.28±13.51) min and (40.38±18.75) min, respectively ( P>0.05). The postoperative pain scores were 2.49±1.23 and 3.02±1.48, respectively ( t=5.05, P<0.001). The average postoperative hospital stays were (2.87±0.93) d and (3.80±1.31) d, respectively ( t=11.05, P<0.001). The postoperative Kiyak satisfaction scores were 4.31±0.66 and 4.15±0.63, respectively ( t=2.93, P=0.004). Conclusion:The safety of modified Trocar approach is comparable to that of conventional three-hole approach. The modified approach showed a shorter postoperative hospital stay, less pain, better scars, and higher patient satisfaction.

The policy system for the construction and management of public hospital with multiple districts is gradually being established and improved,the game among stakeholders affects the effect of policy implementation.There are differences in the strictness of policy implementation on national and local health commission,deviations between local government urban development requirements and the hospital's own construction goals in the process of policy implementation.Based on the game theory of public policy implementation,it analyzes the influencing factors of one hospital with multiple districts and the focus issues encountered in policy implementation,put forward management suggestions for health commission and public hospitals.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

The policy system for the construction and management of public hospital with multiple districts is gradually being established and improved,the game among stakeholders affects the effect of policy implementation.There are differences in the strictness of policy implementation on national and local health commission,deviations between local government urban development requirements and the hospital's own construction goals in the process of policy implementation.Based on the game theory of public policy implementation,it analyzes the influencing factors of one hospital with multiple districts and the focus issues encountered in policy implementation,put forward management suggestions for health commission and public hospitals.