Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.

Objective To investigate the clinical value of thromboelastography (TEG) in monitoring the coagulation function change after plasma supplementation in the patients with severe liver cirrhosis diges-tive tract hemorrhage.Methods A total of 48 patients with high risk and extreme high risk liver cirrhosis a-cute upper digestive hemorrhage receiving the treatment in ICU of this hospital from February 2020 to March 2023 were selected as the study subjects.After plasma infusion with the dose of 10 mL/kg,the coagulation function status was detected.The patients were divided into the TEG group (n=20) and the control group (n=28) according to different detection modes of coagulation function.The TEG group simultaneously detec-ted TEG and traditional coagulation function detection,while the control group only conducted the traditional coagulation detection.TEG and coagulation function detection indicators after the infusion of plasma were compared between the two groups.The plasma infusion amounts at 24 h after admitting in ICU were recorded and the control status of digestive tract hemorrhage was evaluated.Results The R value in the TEG group was (8.02±6.09)min,the K vale was 2.5(1.3,5.0)min,the coagulation comprehensive index (CI) was-4.70±6.29,the maximal shear stress coefficient (MA) was 50.35±18.84,LY30 was 0.The Pearson corre-lation analysis showed that MA was positively correlated with FIB and PLT (r=0.470,0.526,P<0.05),and the other indexes had no correlation.Compared with the control group,the plasma infusion amounts in the TEG group was more[(419.00±143.18)mL vs. (400.00±137.54)mL],the digestive tract hemorrhage con-trol rate was higher[75.00％(15/20) vs. 53.57％(15/28)],but the differences were not statistically signifi-cant (P>0.05).The multiple linear regression was MA=-3.427+11.200×Ln(PLT)+10.230×Ln(FIB).Con-clusion In the patients with severe lever cirrhosis acute upper gastrointestinal bleeding,TEG could earlier find the co-agulation function improvement situation after plasma supplementation than the traditional coagulation detection.

Background and purpose:Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma.High mobility group A2(HMGA2)has been proven to play an important role in the occurrence and development of various tumors,but its biological functions in leptomeningeal metastatic melanoma cells remain unclear.On the basis of building mouse models of central nervous system metastasis of melanoma,this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells,primary site melanoma cells and brain parenchymal metastatic melanoma cells,and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells.Methods:B16 mouse melanoma cells(B16-parental cells,B16-Par)stably expressing tdTomato and luciferase were generated by lentiviral infection.Subsequently,B16 specific brain parenchymal metastatic cells(B16-brain metastatic cells,B16-BrM)and B16 specific leptomeningeal metastatic cells(B16-leptomeningeal metastatic cells,B16-LM)were collected after adaptive screening of metastatic sites in vivo.The differences in migration and proliferation among B16-Par,B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8(CCK-8).RNA sequencing(RNA-seq)was used to analyze differential gene expression in B16-Par,B16-BrM and B16-LM,and HMGA2 gene specifically upregulated in B16-LM was screened out.The results were verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Gene ontology(GO)analysis was performed for genes which were upregulated in B16-LM specifically.siRNA was used to interfere with the expression of HMGA2 gene in B16-LM,and the knock-down effect was verified by RTFQ-PCR and Western blot.The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay.Using GSE174401 data in Gene Expression Omnibus(GEO),the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified.Results:Compared with Par cells,tumor cells screened by the brain environment were more likely to colonize the central nervous system.B16-LM had stronger migration and proliferation abilities,and upregulated the expression of HMGA2 gene.GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation.When the expression of HMGA2 gene was knocked down,the migration and proliferation of B16-LM could be inhibited.HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients.Conclusion:Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics,which promoted cell migration and proliferation by upregulating HMGA2 gene expression.

Objective:To evaluate the efficacy of apatinib combined with 131I therapy for progressive metastatic differentiated thyroid cancer (pmDTC). Methods:Seven patients (1 male, 6 females, age: 58(51, 66) years) with pmDTC in Nanjing First Hospital between November 2017 and February 2022 were enrolled. Patients received oral apatinib 500 mg once daily. The effect of apatinib on differentiated thyroid cancer were evaluated by using 18F-FDG PET/CT or CT at 3(2, 4) months after the treatment. Then in the state of continuous administration of apatinib, 131I therapy was initiated. 18F-FDG PET/CT or CT was performed at 3 months after apatinib combined with 131I therapy to evaluate the response. Both thyroglobulin (Tg) and Tg antibody levels were monitored every 4 to 8 weeks after the treatment. Wilcoxon signed-rank test was used for data analysis. Results:Five patients achieved partial response after 3(2, 4) months of apatinib treatment and two patients had progressive disease. The disease control rate and objective response rate were both 5/7. Five patients achieved partial response and two patients were in stable disease after apatinib combined with 131I therapy for 2(1, 2) times, with disease control rate and objective response rate of 7/7 and 5/7, respectively. The Tg level declined from 8 644(2 504, 16 300) μg/L (baseline) to 143(7, 3 574) μg/L( z=-2.37, P=0.018) after apatinib combined with 131I therapy. In addition, one patient had a significant increase in 131I uptake in the tumor lesions after long-term treatment with apatinib. Conclusions:Apatinib has obvious anti-tumor effects and high objective response rate is observed after apatinib treatment in patients with pmDTC. The anti-tumor effects are more prominent after combined with 131I therapy. Long-term treatment with apatinib may alter the tumor microenvironment to induce differentiation and increase iodine uptake in tumor lesions, which need to be further studied.

Objective: To analyze the childhood blood pressure (BP) trajectory and its relationship with overweight and obesity, to provide evidence regarding prevention and control of childhood elevated BP. Methods: A total of 1 177 children who participated in five surveys of Zigong school based cardiometabolic risks survey. Elevated BP was defined by using National BP reference for Chinese children. Groupbased trajectory model was used to identify distinct BP trajectories. Logistic models were conducted to investigate the association of number of overweight/obesity across surveys with BP trajectory. Results: In the five consecutive waves, the corresponding prevalence of elevated BP was 1.9%, 6.6%, 7.0%, 12.5% and 11.2%. Childhood BP trajectory were classified into constant low and high increasing risk of elevated BP groups. The risk of elevated BP increased at a steady rate with age in constant low risk of elevated BP groups, while the risk of elevated BP increased dramatically with age in high increasing risk of elevated BP groups. Logistic regression analysis showed that those with increasing number of occurrence of overweight/obesity tended to be classified into high increasing risk of elevated BP group( OR=1.34, 95%CI=1.17-1.53, P <0.01). Conclusion Blood pressure trajectory during childhood varies. The risk of elevated BP increased dramatically with age in overweight and obese children. Attention should be paid to the BP trajectory of overweight and obese children to prevent elevated BP.

Objective:To analyze the horizontal scientific research projects from 2015 to 2019 by the provincial Centers for Disease Control and Prevention (CDC) in China, and to compare the regional differences, in order to provide the suggestion on the scientific management of CDC.Methods:The horizontal scientific research projects from 2015 to 2019 were retrospectively analyzed by questionnaire survey. Multiple linear regression models were adopted to examine the trend, and variance analyses were used to test the differences in horizontal scientific research projects among the Eastern, Central, and Western regions.Results:From 2015 to 2019, provincial CDC have received RMB 124.3 million of horizontal scientific research project funds totally, of which 51.9% were funded by enterprises, and 86.9% were undertaken by provincial CDC themselves. There were no statistical significance in the change of research project funds obtained by provincial CDC ( F=0.46, P = 0.764) during this period.The number of horizontal scientific research projects undertook or participated by provincial CDC in the Eastern region were more than that of the Central and Western region ( F = 5.85, P = 0.004; F = 5.03, P = 0.008). Conclusions:The horizontal scientific research projects obtained by the provincial CDC remained stable in recent years while distribution was unbalanced in the region areas. It is suggested to innovate the management mode of scientific research projects with strengthening the trans-agency, trans-department and trans-regional cooperation.

【Objective】 To analyze the risk factors of anemia in premature infants and the status of blood transfusion. 【Methods】 Clinical data of preterm infants with age ≤48 hours and hospitalization time ≥7 days, admitted to our hospital from August 2018 to July 2019, were collected. According to the Hb value, they were divided into the anemia group and the non-anemia group. The general information, disease occurrence, and treatment measures during hospitalization of the two groups were compared, and the risk factors affecting anemia were analyzed. 【Results】 A total of 169 cases were included in this study, including 88 cases in the anemia group and 81 cases in the non-anemia group. There were statistically significant differences between two groups in assisted reproduction 47(53.409) vs 33(40.741), basic Hb value 180.395(176.282, 184.508) vs 162.841(158.596, 167.085), maternal pregnancy anemia 27(30.682) vs 12(14.815), late-onset sepsis(LOS) 64(72.727) vs 31(38.272), mechanical ventilation 46(52.273) vs 10(12.346), neonatal respiratory distress syndrome(NRDS) 51(57.955) vs 26(32.099), coagulation dysfunction 27(30.682) vs 11(13.580) and average hospitalization days 31.276(26.885, 35.666) vs 15.798(14.251, 17.344), all P<0.05. Multivariate logistic results showed assisted reproduction, maternal pregnancy anemia, mechanical ventilation, coagulation dysfunction and average hospitalization days ≥20 were risk factors for preterm anemia. A total of 40 cases(23.669%) needed RBC transfusion to correct anemia during hospitalization, including 21 cases of very low birth weight infants(VLBWI). 8 patients(38.095%) received RBC transfusion ≥3 times during VLBWI hospitalization. The incidence of bronchopulmonary dysplasia(BPD) in the multiple transfusion group(≥3 times of RBC transfusion) was higher than in the non-multiple transfusion group. 【Conclusion】 Maternal anemia during pregnancy, assisted reproduction, mechanical ventilation, coagulation dysfunction and average hospitalization days are the related factors affecting the occurrence of anemia. The occurrence of BPD may be associated with multiple blood transfusions, but there is no clear evidence to prove that blood transfusion is an independent risk factor for the development of BPD, and a large sample, multi-center study is needed.

Objective:To explore the clinical application value of MRI in quantitative evaluation of anterior cruciate ligament mucoid degeneration (ACL-MD).Methods:From March to July 2020, 40 patients who were scheduled to undergo arthroscopic treatment were prospectively collected in the First Affiliated Hospital of Kunming Medical University.The anterior cruciate ligament tissue from the lateral edge of the tibial end was taken during the operation. Based on the pathologicalre sults, the patients were divided into the ACL-MD group ( n=19) and the normal group ( n=21). The sagittal plane three-dimensional steady-state rapid precession (3D-FIESTA), T 1 mapping, T 2 mapping, and T 2* mapping were performed before the knee joint surgery, and the scanned images were post-processed and analyzed to measure the T 1, T 2, and T 2* values of the tibial end of the anterior cruciate ligament.The relaxation time of the ACL-MD group and the normal group was compared using independent sample t test. The ROC curve was drawn using each parameter and the areas under the curve (AUC) for the diagnosis of ACL-MD were obtained.DeLong test was used to compare the differences of AUCs. Results:The T 1 [(1 291.9±273.4) ms], T 2 [(54.8±10.6) ms], and T 2* values [(30.6±6.4) ms] of anterior cruciate ligaments in the ACL-MD group were significantly higher than those in the normal group [ (1 087.0±121.0), (44.8±7.1), (20.4±4.8) ms; t=3.011, 3.473, 5.658, all P<0.001]. The AUCs of T 1, T 2, T 2* were 0.747, 0.764, 0.912, sensitivity of 63.2%, 63.2%, 100%, and the specificity of 100%, 95.2%, 76.2% in diagnosing ACL-MD. The AUC of the T 2* value was higher than those of the T 1 and T 2 values, and the differences were statistically significant ( Z=1.734, 2.162, P=0.043, 0.031). Conclusion:T 1, T 2, T 2*values measured by MRI quantitative imaging have high performance in assessing knee joint ACL-MD, and T 2* value has the largest AUC and the highest diagnostic efficiency.

Objective: To understand the association between childhood abuse experience and health risk behaviors among college students, providing references for childhood abuse and health risk behavior prevention. Methods: During Mar. to Apr. of 2016, 918 college students from 2 universities in Nanchong city were selected through cluster sampling, the survey included general demographic characteristics, childhood abuse experiences and health risk behaviors. Chi square test was used for univariate analysis, and Logistic regression was used for multivariate analysis. Results: A total of 720(78.43%) of participants reported at least one type of health risk behaviors, overeating was the most common type[595(64.81%)]. The number of adolescent reporting smoking, drinking 5 or more beers at a time, fighting and suicidal ideation was 146(15.90%), 271(29.52%), 224(24.40%), 205( 22.33 %), respectively. Multivariate Logistic regression analysis showed that a significant positive association between experiencing at least one kind of childhood abuse and the behaviors of fighting, suicidal ideation, and overeating; between childhood emotional neglect with smoking and suicidal ideation; between childhood emotional abuse with fighting, suicidal ideation, and overeating; and between childhood sexual abuse with smoking( P <0.05). Conclusion Health risk behavior in college students is popular. Childhood abuse can increase the risk of health risk behaviors of college students.

OBJECTIVE：To study the effect s of Bifidobacterium combined with L-carnitine on intestinal flora of dysbacteriosis diarrhea model rats. METHODS ：Totally 30 SD rats were randomly divided into blank control group ，model group ，probiotics group（Bifidobacterium triple viable enteric coated capsules 70 mg/mL），L-carnitine group （L-carnitine injection 50 mg/mL）and L-carnitine+probiotics group （L-carnitine injection 50 mg/mL+Bifidobacterium triple viable enteric coated capsules 70 mg/mL）. Except for blank control group ，the rats in other groups were given 50 mg/mL clindamycin phosphate intragastrically （2 mL/rat， once a day ，for 4 consecutive days ）to establish the model of dysbacteriosis diarrhea. On the 5th day of the experiment ，the rats in administration groups were given corresponding drugs intragastrically ，blank control group and model group were given equal volume of normal saline intragastrically ；with the dosage volume of 1 mL/rat，once a day ，for consecutive 7 days. The general situation of rats in each group was observed during the experiment. The feces of normal control group and model group at the end of the modeling and the feces of the rats in administration group after the last administration were collected for genomic DNA extraction，polymerase chain reaction amplification ，library construction and high-throughput sequencing. After processing ，the effective data were analyzed by operational taxonomic unitsclustering and species annotation ，as well as Alpha and Beta diversity of compared with blank control group ，grade 1 feces and grade 2feces were found in model group. The diversity and richness of intestinal flora ，the ratio of Firmicutes/Bacteroidetes and zhongjuanwang7@163.com the abundance of probiotics such as Lactobacillus， Bifidobacterium and Ackermann were significantly decreased （P＜0.05），while the abundance of pathogenic bacteria such as Enterococcus was significantly increased （P＜0.05）. At the end of the recovery period ，compared with model group ，the activity，fecal morphology and color of rats in probiotics group ，L-carnitine group and L-carnitine+probiotics group returned to normal，and the diversity and richness of intestinal flora had no significant difference （P＞0.05）. However ，the abundance of Lactobacillus in intestinal tract was increased to a certain extent ，and the abundance of Ackermann in intestinal tract of rats in L-carnitine+probiotics group was significantly increased （P＜0.05）. CONCLUSIONS ：Although Bifidobacterium combined with L-carnitine have no significant effect on improving the diversity and richness of intestinal flora in dysbacteriosis diarrhea model rats，it could increase the abundance of probiotics to a certain extent.