Objective:To assess the clinical efficacy and safety of image-guided γ-ray stereotactic body radiation therapy(IG γ-SBRT)in treating advanced pancreatic cancer.Methods:A total of fifty-six patients with advanced pancreatic cancer admitted to Senior Department of Oncology Medicine of the Fifth Medical Center of Chinese PLA General Hospital(Department of Oncology of the Sixth Medical Center)from February 2017 to September 2020 were selected.All patients were treated with IG γ-SBRT,and the 50%-60%of isodose curve covered the planned target volume(PTV).The peripheral dose of each time was 3.0-4.5 Gy,and there were 10-11 times of treatment.The therapeutic effect was observed and was evaluated by follow-up.The visual analog scale(VAS)score was adopted to assess the situation of the pain of patients before and 3 months after treatment,and the adverse reaction of them.Results:In the 56 patients,52 cases occurred epigastric pain with VAS ranging from 3 to 10 points,among which 32 patients accompanied by symptoms such as lower back pain and abdominal distension.After 3 months of treatment,the results of reexamination and follow-up indicated that there were 48 patients whose VAS scores decreased 3 scores and above 3 scores on the basis of original scores,and the efficiency of treating pain was 92.3%.In addition,the VAS scores of 3 patients decreased 1-2 scores on the basis of original scores,which ratio was 5.85%of the total number of people.All 56 patients were reexamined at the 3rd month after treatment,and 13 cases of them obtained complete response(CR),and 37 cases obtained partial response(PR),and 1 case obtained progressive disease(PD),and 5 cases obtained stable disease(SD),and the objectively response rate(ORR)was 89.3%,and the locally control rate was 98.2%.In addition,median progression-free survival(PFS)was 6.5 months,and 1-year survival rate was 62.5%(35/56),and 2-year survival rate was 23.2%(13/56).The adverse reactions of 56 patients were the adverse reactions of digestive system and blood system,among which 47 patients occurred upper digestive tract reaction,and the incidence of adverse reactions was 83.9%(47/56).A total of 43 patients occurred myelosuppression,and the incidence of myelosuppression was 76.8%(43/56).Conclusion:IG γ-SBRT can effectively relieve the symptoms of metastatic pancreatic cancer,and improve the effectiveness of treatment,the local control rate and survival rate.The tolerance of adverse reaction of that is favorable,and the safety of that is higher.

Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (P < 0.05). No significant difference in serum FABP4 levels was found among the three groups (P>0.05). The levels of serum parathyroid hormone (PTH), alkaline phosphatase (ALP), type Ⅰ procollagen amino-terminal propeptide (PⅠNP), type Ⅰ collagen cross-linked C-terminal peptide (CTXⅠ), and bone-specific alkaline phosphatase (BALP) in the OP group were higher than those in the ON group and the normal bone mass group (P < 0.05). Lumbar post-menopause BMD was positively correlated with serum Apelin-13 levels (P < 0.05), but had no correlation with serum FABP4 levels (P>0.05). Lumbar BMD was negatively correlated with serum PTH, ALP, PⅠNP, CTXⅠ, BALP, and age (P < 0.05), but positively correlated with body weight, body mass index, T-score, fasting insulin, and insulin resistance index (P < 0.05). Multivariate Logistic regression analysis showed that serum Apelin-13, PTH, ALP, PⅠNP, CTXⅠ, and BALP levels were independent factors influencing the occurrence of OP in postmenopausal women (P < 0.05). ROC curve results showed that the optimal cut-off value of serum Apelin-13 for predicting PMOP was 18.51 pg/mL, with an area under the curve of 0.716, a sensitivity of 70.0%, and a specificity of 64.4%. Conclusion Apelin-13 is lowly expressed in the serum of PMOP patients, and its expression level is closely related to lumbar BMD, which may serve as an early screening indicator and potential therapeutic target for PMOP.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.

ObjectiveTo observe the effect of aqueous extract of Sophorae Tonkinensis Radix et Rhizoma （STRR） on rheumatoid arthritis （RA） and to explore the anti-bone destruction mechanism based on phosphatidylinositol 3-kinase （PI3K）/serine/threonine-protein kinase （Akt） pathway. MethodHigh-performance liquid chromatography （HPLC） was used to determine the content of main active components in aqueous extract of STRR， and type Ⅱ collagen to induce RA （CIA） in mice. The blank group， model group， methotrexate （MTX） group （0.5 mg·kg^-1）， and low-dose （100 mg·kg^-1） and high-dose （200 mg·kg^-1） STRR aqueous extract groups were designed. Joint swelling was observed and clinical scores of CIA mice were calculated. Pathological changes of mouse joints were observed based on hematoxylin and eosin （HE） staining， and Micro-CT was performed to monitor joint destruction. TRAP staining was used to observe osteoclast formation in mouse joint， and Western blot to detect the expression of key proteins in PI3K/Akt signaling pathway in mouse joint tissue. ResultThe model group demonstrated higher degree of joint swelling， clinical scores of CIA， and degrees of synovial hyperplasia， inflammatory cell infiltration （P<0.01）， and joint destruction， more osteoclasts， and higher levels of matrix metallopeptidase-9 （MMP-9）， cathepsin K （CTSK）， nuclear factor of activated T-cells cytoplasmic 1 （NFATc1）， PI3K， and phosphorylated-Akt （p-Akt） proteins than the blank group （P<0.01）. Compared with the model group， the low-dose and high-dose aqueous extract of STRR alleviated joint swelling， reduced the clinical scores of CIA mice （P<0.05， P<0.01）， relieved the pathological changes of joint tissue （P<0.01） and joint destruction， decreased osteoclasts （P<0.05， P<0.01）， and lowered the levels of PI3K/Akt signaling pathway-related proteins in joint tissue of mice （P<0.01）. ConclusionThe aqueous extract of STRR can significantly delay the inflammatory response of RA and especially inhibit bone destruction by down-regulating the PI3K/Akt signaling pathway.

ObjectiveTo investigate the therapeutic effect of Qingmei compound on acute gouty arthritis （AGA） in rats and preliminarily clarify its mechanism. MethodForty male SD rats were randomly divided into a blank group， a model group， a colchicine group （0.3 mg·kg^-1）， and low- and high-dose Qingmei compound groups （200 and 400 mg·kg^-1）， with eight rats in each group. The AGA model was induced by injecting 50 g·L^-1 monosodium urate （MSU） into the ankle joint of the rats except those in the blank group. The ankle swelling index was measured before and 6， 24， and 48 h after modeling. The pathological changes in the joint tissues of AGA rats were observed by hematoxylin-eosin （HE） staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the joint tissues of rats was detected by immunohistochemistry. The protein expression of NOD-like receptor protein 3 （NLRP3） pathway and key proteins in the joint tissues of rats was detected by Western blot. ResultCompared with the blank group， the model group showed increased ankle swelling index， synovial hyperplasia， and inflammatory infiltration， and up-regulated expression of IL-1β， TNF-α， and NLRP3 proteins in the ankle joint and the ratio of Caspase-1 shear body to Caspase-1 precursor protein （Caspase-1 p20/Caspase-1） （P<0.01）. Compared with the model group， the Qingmei compound groups showed reduced ankle swelling index of AGA rats， especially the low-dose Qingmei compound group （P<0.01）. Meanwhile， Qingmei compound inhibited synovial hyperplasia and inflammatory infiltration （P<0.01） and reduced the levels of IL-1β， TNF-α， and NLRP3 proteins and Caspase-1 p20/Caspase-1 in joint tissues （P<0.01）. ConclusionQingmei Compound can significantly alleviate the joint swelling and inflammatory infiltration of AGA， and its mechanism may be related to the inhibition of the NLRP3 signaling pathway.

Objective:To preliminarily study the feasibility, safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with selective portal vein embolization (SPVE) before surgical resection in the treatment of large liver cancer.Methods:A retrospective study was conducted on the clinical data of 17 patients with large liver cancer treated with TACE combined with SPVE from January 2016 to December 2019 at the Department of Hepatobiliary Surgery, the Sixth Medical Center of PLA General Hospital. The study included 15 males and 2 females, aged (59.17±10.30) years. The levels of alanine aminotransferase, tumor changes and patient survival were analyzed before operation, after TACE, and after SPVE.Results:Among the 17 patients, the levels of alanine aminotransferase on the 1st and 3rd day after SPVE was significantly higher than those after TACE [191.4 (30.5-1966.4) IU/L vs 125.3 (35.7-846.2) IU/L on the first day, and 298.5 (24.6-1334.2) IU/L vs 208.6 (21.6-775.6) IU/L on the 3rd day], all P<0.05. One month after the two combined embolism, among the 6 patients with a tumor diameter of 5-10 cm, 2 patients (33.3%) had complete remission, 3 patients (50.0%) had partial remission, and 1 patients (16.6%) had stable disease. For the tumor’s longest diameter, among the 11 patients with tumors >10 cm, 1 patient had complete remission (9.1%), 4 patients had partial remission (36.4%), 5 patients had stable diseases (45.5%), and 1 patient had disease progression (9.1%). Eventually, 11 patients underwent surgical exploration. The median residual liver volume before treatment was 329.5 (284.9-365.7) ml, and after the combined procedure 415.6 (354.7-718.8) ml. The median hyperplasia ratio was 28.1% (14.1%-51.3%). Eight patients finally underwent surgical resection. There was no death in the perioperative periods. The median tumor-free survival time was 17 (7-42) months, and the median survival time was 27 (7-42) months. Conclusion:For patients with large liver cancer with insufficient remnant liver volume, preoperative TACE+ SPVE has certain value in controlling tumor progression, promoting remnant liver hyperplasia, increasing surgical resection rate and improving prognosis.

Objective:To analyze the effect of home quarantine on blood glucose and lipids in healthy adults during the COVID-19 epidemic times.Method:From April 7, 2020 to May 1, 2020, 512 adults wereexamined in Beijing physical examination center, of which 87 adults aged olderthan 18, received community closed management or home quarantine from January 23, 2020 to March 30, 2020, and theadultshad physical examination in Beijing physical examination center in the same month of 2018 and 2019 were selected as controls. The change trend of blood glucose and blood lipid acrossthe three years was analyzed by one-way repeated measurement of variance, and the difference of blood lipid and blood glucose between two years of physical examination was further analyzed by Bonferroni method. Datawereanalyzed by gender.Result:Among the 87 subjects, 36 (41.4%) were male and 51(58.6%) were female. The average age was (46.3±13.2) years and ranged from 24 to 74. The difference of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting blood glucose (FBG) among 2018, 2019 and 2020 was statistically significant (all P<0.05), while differences in LDL-C, TC and FBG were statistically significant for males (all P<0.05) and HDL-C, LDL-C, TC and FBG were statistically significant for females (all P<0.05). HDL-C in 2018and 2020were significantly lower than that in 2019 [(1.27±0.29), (1.30±0.31) vs. (1.36±0.34) mmol/L], LDL-C in 2020was significantly higher than that in 2018and 2019 [(3.11±0.88) vs. (2.81±0.77), (2.84±0.71) mmol/L], TG in 2020 was significantly higher than that in 2019[(1.54±1.17) vs. (1.32±0.80) mmol/L], TC in 2019and 2020were significantly higher than that in 2018 [(4.88±0.94), (5.10±0.99) vs. (4.63±0.90) mmol/L], and the FBG in 2019and 2020were significantly lower than that in 2018 [(5.34±1.17), (5.44±1.58) vs. (5.84±1.70) mmol/L] (all P<0.05). The comparative analysis of men and women showed that the means of LDL-C, TG, TC and FBG of men were higher than those of women while the mean of HDL-C was lower than that of women in each year; compared with 2019, the increase of LDL-C and TC of men was obvious while the decrease of HDL-C of women was obvious (all P<0.05) in 2020. Conclusion:During the epidemic period of COVID-19, the home quarantine has adverse effects on blood glucose and lipid.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective:To analyze the relationship between molecular cytogenetic abnormalities and clinical characteristics of acute lymphoblastic leukemia (ALL) in childhood .Methods:A total of 403 patients newly diagnosed with ALL in the Department of Hematology, Shanghai Children′s Hospital from January 2009 to December 2018 were enrolled in this study.All the patients had completed the test of bone marrow smear cytology, immunotyping, karyotype analysis, and fluorescence in situ hybridization (FISH).Results:(1)There were 240 males (59.6%) and 163 females (40.4%) aged (5.31±3.46)years.There were 374 patients(92.8%) with B cell acute lymphoblastic leukemia (B-ALL)and 29 patients(7.2%) with T cell acute lymphoblastic leukemia (T-ALL). (2)Cytogenetics: A total of 311 cases (77.2%) showed mitosis in the chromosomal karyotype analysis, of which 126 cases were abnormal (abnormality detection rate was 40.5%), including 15.4% (48/311cases) hyperdiploid.(3)Fusion gene: Positive fusion genes were found in 110 cases (27.3%), including TEL/AML1 gene in 70 cases (17.4%), BCR/ ABL in 13 cases (3.2%), MLL in 19 cases (4.7%). From 2015-2018, 8 cases (4.0%) of PBX1/TCF3 fusion gene, 1 case of EBF1-PDGFRB fusion gene, 6 cases of SIL/TAL1 fusion gene were detected, SIL/TAL1 positive patients which were accounting for 33.3% of T-ALL improved the detection rate of T-ALL molecular abnormalities.Patients with positive BCR/ ABL were older than those with positive TEL/AML1 and positive MLL[(8.01±3.11) years vs.(3.89±1.84) years, (1.56±1.25) years, P<0.001]; patients with positive PBX1/TCF3 [6.58±4.83) years]were older than those with positive TEL/AML1 and positive MLL (all P<0.05); patients with positive MLL were younger than those with positive TEL/AML1 [(1.56±1.25) years vs.(3.89±1.84) years, P=0.001]; the white blood cell (WBC) count of positive MLL patients was higher than that of positive TEL/AML1 and positive BCR/ ABL patients [(76.97±19.87)×10 9/L vs.(16.94±2.28)×10 9/L, P=0.002; (76.97±19.87)×10 9/L vs.(20.53±6.49)×10 9/L, P<0.05]; the WBC count of PBX1/TCF3 positive children was higher than that of positive TEL/AML1 patients [(85.75±30.32)×10 9/L vs.(16.94±2.28)×10 9/L, P=0.002]. The immunotyping of positive MLL patients was dominated by early precursor B-ALL (14/19 cases), while the immunotyping of TEL/AML1 and BCR/ABL positive patients were dominated by common-B-ALL(57/70 cases and 11/15 cases). (4)The detection rates of chromosome karyotype analysis, FISH, and polymerase chain reaction (PCR) were used to detect molecular genetic abnormalities in primary ALL patients, the detection rate was 40.5% (126/403 cases), 69.2% (279/403 cases), and 29.7% (60/202 cases), respectively.The difference was statistically significant ( P<0.001). There was no significant difference in the abnormality detection rate between chromosome karyotype analysis and PCR ( P=0.71). (5)There was no significant difference in the detection rate of molecular cytogenetic abnormalities between different genders and age groups ( P=0.651, 0.721). There was a significant difference between the WBC count ≥50 × 10 9/L group and <50 × 10 9/L group(37/51 cases vs.107/352 cases, P<0.001). The detection rate of B-ALL genetic abnormalities was higher than that of T-ALL genetic abnormalities(275/374 cases vs.14/29 cases, P=0.005). Conclusions:There are a higher proportion of hyperdiploidy chromosomes in children ALL.The distribution of fusion genes is related to age, primary white blood cell count, and immunotyping.The three detection methods complement each other and greatly improve the detection rate of genetic abnormalities.The detection rate of T-ALL genetic abnormality is low, and new detection methods may be needed.