OBJECTIVE To predict the possible impact of pembrolizumab（PEM） as a first-line drug after being included in the national medical insurance system in the treatment of advanced or metastatic non-small cell lung cancer based on real-world data from the perspective of the national medical insurance payer， to provide a basis for the decision-making of the medical insurance department. METHODS A budget impact analysis model was constructed to compare the impact of pembrolizumab not included in medical insurance and included in medical insurance on medical insurance fund expenditure in the next five years（ 2024- 2028） with 2023 as the baseline year. The target population was the patients with EGFR gene mutation-negative and anaplastic lymphoma kinase （ALK）-negative locally advanced or metastatic non-small cell lung cancer； estimated cost mainly included the cost of drugs， the cost of adverse reaction treatment， the cost of examination， the cost of admission and monitoring， etc； equipment ratio of PEM in 183 hospitals of Guangdong province from 2020 to 2022 was used as the market share. Univariate sensitivity analysis was used to test the robustness of the basic analysis results. RESULTS When PEM was not included in the medical insurance， the medical insurance reimbursement amount of the target population from 2024 to 2028 was 4 933 623.5 thousand yuan-5 151 198.3 thousand yuan， respectively. If PEM was included in the medical insurance， the above data were 11 871 972.2 thousand yuan-14 540 571.0 thousand yuan， respectively； the increase in medical insurance reimbursement under the two scenarios was 6 720 773.9 thousand yuan-9 606 947.5 thousand yuan， respectively. The proportion of medical insurance reimbursement to the medical insurance expenditure of the year after PEM was included in medical insurance was 0.298 0%， 0.262 1%， 0.228 8%， 0.208 2%， and 0.185 7%， respectively. The increase in medical insurance reimbursement accounted for 1.084 0%， 0.995 7%， 0.888 6%， 0.886 3%， and 0.861 6% of the increase in the expenditure of the medical insurance fund in the current year， all of which showed a decreasing trend year by year. CONCLUSIONS If PEM is included in medical insurance， due to its high unit price， the medical expenditure will increase accordingly， which will have a great impact on the medical insurance fund expenditure. However， when the drug is used in patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic non-small cell lung cancer， the proportion of the medical insurance reimbursement amount in the current year’s medical insurance fund expenditure and the proportion of the increase in medical insurance reimbursement in the current year’s increase in medical insurance fund expenditure are decreasing year by year.

OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

Objective:To investigate the safety and efficacy of nimotuzumab combined with IMRT radiotherapy in the treatment of elderly patients with locally advanced cervical cancer (LACC).Methods:A retrospective analysis was conducted for 34 elderly LACC patients treated with nimotuzumab combined with IMRT radiotherapy or concurrent chemoradiotherapy in the Zhangzhou Affiliated Hospital of Fujian Medical University from June 2020 to December 2021. The efficacy and side effects were evaluated one and two years after treatment.Results:Median follow-up time was 13.3 months (6.1-24.3 months). A total of 24 cases of complete response (CR) and eight cases of partial response (PR) were achieved after treatment, with an objective response rate (ORR) of 94.1% (32/34). The tumor diameters were (49.56 ± 19.22) mm before treatment and (19.61 ± 14.59) mm after treatment, with a tumor regression rate (TRR) of 59.22%.The 1- and 2- year progression-free survival (PFS) rates were 84.9% and 84.9%, overall survival (OS) rates 91.8% and 87.2%, respectively, disease-free survival (DFS) rates 91.8% and 87.2%, respectively, and the cancer-specific survival (CSS) rates 95.7% and 90.9%, respectively. The main adverse events included radiation enteritis, leukopenia, hypoproteinemia and anemia.Conclusions:Nimotuzumab combined with IMRT radiotherapy or concurrent chemoradiotherapy is safe and effective in the treatment of LACC.

Objective:Iron accumulation is related to the occurrence of postmenopausal osteoporosis. Meanwhile, autophagy abnormality of bone marrow hematopoietic cells is observed in hip osteoporotic fracture. This study is performed to investigate correlation between iron accumulation induced bone loss and hematopoietic autophagy dysfunction to explore the new risk factor of osteoporosis.Methods:Male iron accumulation mice model was established by intraperitoneally injecting ferric ammonium citrate. Serum ferritin and osteogenic indicator P1NP were tested by ELISA. Bone mineral density was measured by micro-CT. Femur and tibia bone marrows were collected for hematopoietic stem and progenitor cells proportion and cell apoptosis analysis. Autolysosome formation was measured by image flow cytometry. We used conditional mouse model Atg7 flox/flox; Vav-Cre(Atg7 -/-) in which Atg7 had been genetically deleted in the hematopoietic system. Bone marrow hematopoietic stem and progenitor cells were collected for RNA sequence. micro-CT scan was conducted for Atg7 -/- femur. Results:Ferritin level of iron accumulation mice was significantly higher than control group( P<0.05). Iron accumulation inhibited P1NP and induced decreased bone mineral density( P<0.05). Iron accumulation bone marrow displayed enhanced hematopoietic stem and progenitor cells proportion( P<0.05), with more cell apoptosis( P<0.05). Hematopoietic autophagy was deteriorated in iron accumulation bone marrow. Transcriptomic profiling showed up-regulation of iron activity in Atg7 -/- mice, with increased iron homeostasis and iron membrane transporter genes, including Lcn2, Tfr2, Slc40a1(Fpn1), Steap3, and Cpox. micro-CT revealed severe bone loss and decreased bone mineral density in Atg7 -/- mice( P<0.05). Conclusion:Iron accumulation induced bone loss is related to inhibition of hematopoietic cells. Hematopoietic autophagy dysfunction is associated with bone loss.

Trauma is the leading cause of death for people under 40 years old in the world. At present, the rescue and treatment system of trauma patients in China is not yet well established, and the mortality of trauma patients is higher than those in the developed countries. Improving the treatment system is the key to reducing the trauma mortality. In order to innovate the service mode of trauma first aid, further promote the establishment of regional trauma first aid system, improve the ability of trauma treatment, reduce the mortality and disability rate of trauma patients in Jiangxi Province, recently Health Commission of Jiangxi Province and the First Affiliated Hospital of Nanchang University have reached a consensus on the establishment of Jiangxi trauma first aid center. In order to provide reference for the construction of trauma treatment system, the author analyzes the following aspects including functional positioning, basic requirements, organization management, and evaluation of core indicators.

Objective By discussing the Achilles tendon rupture line of two different methods of plaster fixation after operation,embodies the advantages of downward legs plaster fixation method when the new operation.Methods From January 2014 to December in the inpatient department for Achilles tendon repair in 34 cases as the control group,krackow suture after upward leg plaster fixation;from January 2015 to December in the inpatient department for Achilles tendon repair in 32 cases of patients as the observation group, the concept of krackow suture after downward leg plaster cast, 6 week of daily life were compared between the two groups at discharge and after the operation,the function of ankle and knee joint situation ability. Results At the time of discharge and 6 weeks after operation,the self-care ability,ankle function and knee joint function of the observation group were better than those of the control group (all P＜0.001).The complication rate in the observation group was lower than that in the control group (P＜0.05).Conclusion The new downward Achilles tendon plaster fixation is superior to the traditional plaster fixation method,can improve the patients'self-care ability,reduce complications,promote the recovery of limb function,promote early rehabilitation of patients.

Objective To explore the changes of type H vessel during the low bone mineral density caused by iron accumulation and discuss its clinical meaning.Methods Ten 8-week old male C57BL/6J mice were used for experiments,and randomly divided into two groups:control group and iron group,and 5 mice in each group.In the iron group,0.1 g/kg of iron dextran was injected intraperitoneally once a week for 8 weeks.The control group was injected with the same amount of saline.The femoral and tibial specimens were examined by microscopic CT scan and bone tissue type H vessel immunohistochemical staining.Liver tissue from the two groups were collected for the content of iron by atomic absorption spectroscopy.All experimental data were analyzed with t-test.Results The content of hepatic iron in mice was significantly higher than that in the control group,which indicating that the model was successfully established.The tibia specimens were collected for immunostaining.The vascular area of type H at metaphyseal regions is 11.24％± 1.76％ in iron group and 30.69％±2.78％ in control group,respectively.There is significant difference between the two groups (P＜0.005).The femur specimens were collected for Micro-CT scan,the value of bone mineral density (BMD),bone volume/tissue volume (BV/TV),trabecular thickness (Tb.Th),trabecular number (Tb.N) and trabecular separation (Tb.Sp) was (0.19±0.013) g/cm3,11.92％±1.199％,(35.66±2.684) μm,(2.36±0.429)/mm and (284.41±23.197) μm in iron group and (0.37±0.023) g/cm3,35.76％± 1.336％,(62.05±2.238) μm,(5.68± 1.039)/mm and (163.23± 13.203) μm in control group,respectively.The differences between the two groups were statistically significant (P＜0.05).Conclusion Iron accumulation can lead to low BMD and suppress type H vessel formation in bone,which might provide a new experimental value for mechanism research on osteoporosis caused by iron accumulation.

Objective: To explore the treatment of senile osteoporotic femoral fractures after using internal fixation of bone cement dry prosthetic. Methods: Twelve patients aged from 74 to 94 years with mean age of (84.0±2.5) years with internal fixation of bone cement dry prosthetic surgery who were treated at Department of Orthopaedics in Nanjing Medical University Affiliated Wuxi Second Hospital between May 2013 and May 2015 were retrospectively analyzed. There were 8 male and 4 female, 10 cases of tumble and 2 cases of traffic injury. The fracture types with AO type included 1 case of A1 type, 5 cases of A2 type, 3 cases of A3 type, 1 case of B1 type, 2 cases of B2 type. The steel plate internal fixation with bone cement dry prosthetic method was chosen to treat senile severe femoral fracture. Postoperative observation of postoperative pain assessment, hip joint activity and walking ability were evaluated. Paired simple t test and Wilcoxon rank sum test were used to compare the differences of pain score and the ability to walk. Results: Twelve cases received an average of (16.0±3.6) months follow-up. The average hospitalization days are (9.0±1.4) days and average of intraoperative time was (68.0±10.6) minutes. Intraoperative blood loss compared to normal was (106.0±24.2) ml. Patients began walking load and activities in two weeks. The gait and joint activities gradually restored and there were no obvious deformity and no loose internal fixation. All of the patients didn′t have fracture shift with breaking plates or screws deformation and have no bone cement reaction. The walking ability was (4.1±0.9) points, the hip joint activities were 98.5°±7.7° and pain scores were 1.22±0.58 by Holden grading standards. The differences of walking ability (Z=-3.126, P<0.05) and pain scores (t=23.047, P<0.001) between pre- and post-operative were statistically significant. One patient had contralateral hip pain, 2 patients had lateral thigh pain, 10 patients returned to preoperative level of activity. Postoperative function recovered satisfactorily, there were statistically differences. Conclusion The treatment of severe osteoporosis fractures by internal fixation with bone cement dry prosthetic is a new and effective method, making patients less pain, improving joint function and walking ability.

ObjectiveTo analyze the clinical outcome of locking plate and hemiarthroplasty in treatment of Neer three- and four-part proximal humeral fractures.Methods A totalof 63 consecutive patients aged over 55 years with Neer three- and four-part proximal humeral fractures were treated surgically from June 2006 to June 2010.In the retrospective study,36 patients were treated by open reduction and locking plate fixation ( locking plate fixation group) and 27 patients treated by hemiarthroplasty (hemiarthroplasty group).Clinical outcomes including operation time,blood loss,visual analog scale ( VAS),Constant-Murley score and complications were evaluated.ResultsThe average 19.7 months follow-up showed complication rate of 28％ in the locking plate group,including one patient with varss malunion,one with axillary nerve injury,one with humeral head necrosis,one with heterotopie calcification and four with impingement syndrome.The complication rate was 24％ in the hemiarthroplasty group,including two patients with tuberosity nonunion,one with tuberosity migration,one with impingement syndrome and one with joint semiluxation.The mean Constant-Murley score of three-part fractures in the locking plate group was ( 76.5 ±5.8) points,better than (69.2 ±7.2) points in the hemiarthroplasty group (P ＜0.05 ).While the two groups showed no significant differences with regards to operation time,blood loss and visual analog scale (VAS).As for the four-part fractures,the mean operation time was shorter and the mean blood loss was less in the hemiarthroplasty group compared with the locking plate group (P ＜0.05),while there were no obvious differences in VAS score and Constant-Murley score between the two groups. Conclusions Both locking plate and hemiarthroplasty are the reliable methods for the three- and four-part proximal humeral fractures.The patients' age,bone quality,fracture type,comminution degree and evaluation of osteonecrosis possibility,are critical for surgery decision.

Objective To discuss the operation skills and clinical effects of C-arm fluoroscopy in arthroscopic reconstruction of anterior cruciate ligament(ACL)with the Ligament Advancement Reinforcement System(LARS)artificial ligaments.Methods The study involved 36 patients with acute ACL rupture treated with the LARS artificial ligaments from June 2006.There were 25 males and 11 females,at age range of 22-51 years(average 28.3 years),involving 19 left knees and 17 right knees.The results of preoperative MRI of all patients suggested discontinuation of ACL,with average score of Lysholm on knee joint for 50.The operation was completed under arthroscope.While the locations of the femoral tunnel portal and the tibial tunnel exit were mainly determined by the C-arm fluoroscopy.The diameter of the LARS artificial ligament was 7.5 mm while that of the interference screw 8 mm.Results All 36 patients were followed up for a mean duration of 18 months(9-20 months).The average Lysholm Score was 52 preoperatively and 92 at the 12th week after operation.The clinical results were graded as excellent in 23 patients,good in nine and fair in four according to the Lysholm's classification,with excellence rate of 89%.Conclusions Arthroscopic reconstruction of anterior cruciate ligament with LARS artifical ligament under C-arm fluoroscopy takes advantages of convenient operation,accurate location and satisfactory clinical effect.