Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

【Objective】 To evaluate the clinical efficacy and safety of platelet-rich plasma(PRP) in acute achilles tendon injury by meta-analysis. 【Methods】 Literature on clinical randomized controlled trial of PRP in the treatment of acute achilles tendon injury from Wanfang database, CNKI, VIP database, The Chinese Biological Literature Database, The Chinese Clinical Trials Registry, PubMed, Embase, Cochrane and The US Clinical Trials Registry as of August 2023 were retrieved. The control group received conventional treatment for acute achilles tendon injury, while PRP treatment group received additional PRP treatment. The primary outcome measure was visual analogue pain scale, and the secondary outcome measures were the achilles tendon fracture score, maximum heel rise height, calf circumference and ankle range of motion. The quality of the literature was assessed using the Cochrane manual, and a meta-analysis of qualified literature was performed using RevMan 5.3 software. 【Results】 Seven articles were finally included, involving 421 patients with acute achilles tendon injury, including 212 patients in the PRP treatment group, and 209 patients in the conventional treatment group. The results of meta-analysis showed that there was no difference between the conventional treatment group and the PRP treatment group in terms of the visual analogue pain scale(SMD=-0.44, 95%CI: -0.94~0.06, P>0.05), calf circumference (MD=1.14, 95% CI: -1.56-3.84, P>0.05), ankle joint toe flexion range of motion (SMD=1.85, 95%CI: -1.38-5.09, P>0.05), ankle dorsiflexion range of motion(SMD=2.61, 95%CI: -0.95-6.17, P>0.05), achilles tendon fracture score (MD=-5.60, 95%CI: -15.36-4.16, P>0.05) and the maximum heel rise height (MD=-2.48, 95%CI: -5.30-0.33, P>0.05). And there was no difference in the incidence of adverse reactions between the two groups (X²=2. 455, P>0.05). 【Conclusion】 PRP injection for acute achilles tendon injury does not improve the biomechanical and clinical outcomes of patients, and the use of PRP does not increase the occurrence of adverse reactions.

Objective:To investigate the effect of vitamin D supplementation on weight loss efficacy and insulin resistance (IR) in obese patients.Methods:It was a randomized controlled trial. A total of 190 obese patients with vitamin D deficiency were selected from the obesity clinic of Tianjin Union Medical Center from March to December in 2023. The patients were divided into control group (95 cases) and vitamin D group (95 cases) according to random number table. The control group was given energy-limited high-protein diet combined with moderate intensity exercise, and the vitamin D group was supplemented with vitamin D on the basis of the control group, 14 000 U/week for 24 weeks. A total of 25 dropped out of the study from the two groups for various reasons. Finally, 79 cases in the control group and 86 cases in the vitamin D group were included in the analysis. Independent sample t test and rank sum test were used to compare serum 25 hydroxyvitamin D [25 (OH) D] level, body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin and glycated hemoglobin (HbA 1c) between the two groups at baseline and after intervention. Homeostasis model insulin resistance index (HOMA-IR) was used to evaluate the degree of insulin resistance (IR), and the effects of vitamin D supplementation on weight loss efficiency and IR in those patients were analyzed. Results:There was no significant differences in serum 25(OH)D level between the two groups before intervention ( P>0.05); the serum 25(OH)D level in the vitamin D group was significantly higher than that in the control group after intervention [(30.90±7.55) vs (16.00±4.34) μg/L] ( t=-15.35, P<0.001). The body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin, HbA 1c, and HOMA-IR were all significantly lower after the intervention than those before the intervention in both groups [control group: (93.32±13.47) vs (98.95±14.31) kg, (33.74±5.09) vs (35.80±5.52) kg/m 2, (39.77±11.87) vs (44.12±12.79) kg, (183.76±40.95) vs (204.01±32.18) m 2, 5.00 (4.55, 5.67) vs 5.24 (4.68, 6.42) mmol/L, 16.78 (13.94, 24.30) vs 22.56 (15.95, 31.2) mU/L, 5.55%±0.53% vs 6.05%±0.99%, 4.11 (3.14, 5.57) vs 5.51 (3.61, 8.49); vitamin D group: (88.14±17.66) vs (104.43±22.02) kg, (31.02±5.10) vs (36.66±5.98) kg/m 2, (35.51±12.87) vs (46.67±13.33) kg, (166.50±49.50) vs (213.64±40.14) m 2, 4.70 (4.35, 5.07) vs 5.17 (4.77, 6.30) mmol/L, 13.18 (9.87, 18.84) vs 21.67 (15.78. 32.74) mU/L, 5.43%±0.48% vs 6.21%±1.22%, 2.88 (1.99, 4.21) vs 5.19 (3.82, 9.27)], and the body weight, body mass index, adiposity, visceral fat area, fasting blood glucose, fasting insulin, and HOMA-IR were all significantly lower in vitamin D group than those in the control group [(88.14±17.66) vs (93.32±13.47) kg, (31.02±5.10) vs (33.74±5.09) kg/m 2, (35.51±12.87) vs (39.77±11.87) kg, (166.50±49.50) vs (183.76±40.95) m 2, 4.70 (4.35, 5.07) vs 5.00 (4.55, 5.67) mmol/L, 13.18 (9.87, 18.84) vs 16.78 (13.94, 24.30) mU/L, and 2.88 (1.99, 4.21) vs 4.11 (3.14, 5.57), respectivley] (all P<0.05). The IR remission rate was significantly higher in the vitamin D group than that in the control group after the intervention (37.3% vs 15.3%) ( χ2=8.071, P=0.002). Conclusion:Supplementation of vitamin D on the basis of energy-limited high-protein diet combined with moderate intensity exercise can significantly improve the efficacy of weight loss and IR in obese patients with vitamin D deficiency.

Objective:To evaluate the effects of electroacupuncture (EA) on the learning and memory function of offspring rats exposed to sevoflurane in late-pregnancy.Methods:Thirty-two SPF healthy Sprague-Dawley pregnant rats at gestational day 18, weighing 260-280 g, were assigned to 4 groups ( n=8 each) using a random number table method: control group (C group), sevoflurane group (Sev group), EA group and sham EA group (SEA group). Sev, SEA and EA groups inhaled 2.5% sevoflurane in 50% oxygen for 6 h. In EA group, Shenting, Baihui, bilateral Quchi, and bilateral Zusanli points were stimulated with an electric stimulator (disperse-dense waves, frequency 2/6 Hz, intensity 1 mA, 20 min per day for 7 consecutive days) starting on postnatal day 21, EA was performed again for 7 days after an interval of 1 day, and the EA treatment lasted for a total of 14 days. Moriss water maze test was performed at 36 days of age to detect the spatial learning and memory function. The offspring rats were sacrificed on postnatal day 42, and the hippocampal tissues were removed for calculation of the dendritic spine density of neurons (after Golgi staining) and for determination of the apoptosis rate (using flow cytometry) and the expression of the two primary forms of brain-derived neurotrophic factor (BDNF), mature (mBDNF) and pro (proBDNF), mBDNF/proBDNF ratio, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) (by Western blot). The mBDNF/proBDNF ratio was calculated. Results:Compared with C group, the escape latency was significantly prolonged, the time of staying at the target platform quadrant was shortened, the frequency of crossing the original platform was reduced, the dendritic spine density of hippocampal neurons and mBDNF/proBDNF ratio were decreased, the expression of TrkB was down-regulated, and the expression of p75NTR was up-regulated in Sev groups ( P<0.05). Compared with the offspring rats of Sev and SEA groups, the escape latency was significantly shortened, the time of staying at the target platform quadrant was prolonged, the frequency of crossing the original platform was increased, the dendritic spine density of hippocampal neurons and mBDNF/proBDNF ratio were increased, the expression of TrkB was up-regulated, and the expression of p75NTR was down-regulated in the offspring rats of EA group ( P<0.05), and no significant change was found in the aforementioned parameters in the offspring rats of SEA group ( P>0.05). There was no significant difference in the apoptosis rate of hippocampal neurons among the offspring rats of the four groups ( P>0.05). Conclusions:EA can improve the learning and memory function of offspring rats exposed to sevoflurane in late-pregnancy, and the mechanism may be related to promoting the conversion of proBDNF to mBDNF and improving neuronal development.

Objective:To construct a new model for assessing insulin resistance(IR) in newly diagnosed type 2 diabetic patients by combining anthropometry parameters and biochemical parameters.Methods:A total of 677 newly diagnosed type 2 diabetic patients were included in this study. Clinical data, biochemical indicators, and body composition measurements were collected, and a predictive model was constructed using logistic regression analysis.Results:The IR prediction model was constructed based on five indicators: triglycerides(TG), fasting plasma glucose(FPG), visceral fat area(VFA), alanine aminotransferase(ALT), and uric acid(UA). The formula for the new predictive model was as follows: y=-17.765+ 1.389×ln VFA+ 1.045×ln UA+ 0.91×ln ALT+ 2.167×ln FPG+ 0.805×ln TG. The receiver operating characteristic curve(ROC) area under the curve(AUC) for the model was 0.82, with an optimal cutoff value of 1.67, sensitivity of 0.80, and specificity of 0.71. The AUC values for the triglyceride glucose(TyG) index, lipid accumulation product(LAP), and triglyceride/high-density lipoprotein cholesterol ratio(THR) were 0.75, 0.75, and 0.70, respectively. The corresponding sensitivities were 0.66, 0.84, and 0.71, and the specificities were 0.71, 0.59, and 0.60. The optimal cutoff values were 1.81, 30.31, and 1.14, respectively. Conclusion:The new model constructed using TG, FPG, VFA, ALT, and UA as indicators showed high predictive value and can serve as a new model for assessing IR in newly diagnosed type 2 diabetic patients.

Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.

OBJECTIVE To observe the toxic effects of single administration and repeated administration of Qingzi granules for 13 weeks on rats, and to evaluate their preclinical safety. METHODS For the single dose toxicity experiment, SD rats were randomly divided into two groups, vehicle control group(deionized water) and Qingzi group(18 g·kg-1), which were given in a volume of 30 mL·kg-1 per time, twice in 24 h(interval more than 4 h), and observation was performed for 14 d after administration. The toxicity reaction was evaluated through observation of body weight change and pathological anatomy. For the repeated dose toxicity experiment, juvenile SD rats(postnatal day, PND 4) were randomly divided into vehicle control group (deionized water) and low, medium and high dose of Qingzi groups(1, 2 and 4 g·kg-1). The rats were orally administered twice daily with vehicle or Qingzi for 13 weeks in a volume of 10 mL·kg-1 per time. A recovery period of 4 weeks was followed. Test items included clinical observations, body weight measurement, food intake measurement, hematology test, biochemical test, urinalysis, sex hormone level determination, cellular immune function assay, growth indexes and histopathology test. RESULTS For the single dose toxicity experiment, Qingzi granules were orally administered to SD rats without significant toxicity, and the maximum-tolerated dose was greater than 18 g·kg-1. In the repeated dose toxicity test, juvenile SD rats were given Qingzi granules by gavage and repeated administration for 13 weeks, the no observed adverse effect level was 2 g·kg-1. The target organ of toxicity was the liver and the main toxic effect was inflammatory necrosis of hepatocytes, no dose-dependent relationship. CONCLUSION No overt toxicity of Qingzi granules was observed on the tested animals within the intended clinical dosage range.

Objective:To investigate the incidence, clinical characteristics and risk factors for hip fractures in patients within two years after stroke onset.Methods:A total of 332 persons with first-onset stroke from the neurology department of our hospital between 1 June 2013 and 31 December 2014 were recruited and were divided into the hip fracture group and the non-hip fracture group.Clinical characteristics were recorded.Vision was tested as normal or impaired.Patients were accessed by the National Institutes of Health Stroke Scale(NIHSS), Behavioral Inattention Test, Baking Tray Task, Mini-Mental State Examination(MMSE), Birgitta Lindmark(BL)motor assessment scale, Berg Balance Scale(BBS), Timed Up & Go(TUG)Scale, and Stops Walking When Talking(SWWT)Scale.The clinic characteristics and risk factors for hip fractures were compared between the two groups after a 2-year follow-up.The accuracy of risk factors for fracture prediction was assessed by the sensitivity, specificity, and positive and negative predictive values.Results:Of 332 patients with stroke, 16 cases fractured their hips within two years after stroke onset, which corresponded to an incidence of 33‰/year(95% CI: 15‰/year-50‰/year). The 2-year mortality rate was 44%(95% CI: 25%-60%)and 48%(95% CI: 42%-54%)in patients with and without hip fractures respectively( χ2=0.036, P=0.724). The mean survival time for patients with and without hip fracture was 2.72 years(95% CI: 1.45-2.79)and 2.21 years(95% CI: 1.48-2.34)respectively.The proportions of patients with previous fractures history( χ2=16.780, P=0.041)and impaired vision( χ2=11.210, P=0.027), MMSE scale score( U=14.220, P=0.031), TUG ≥ 15 s( χ2=18.560, P=0.000)were higher, and SWWT( χ2=20.340, P=0.000)was lower in the hip fracture group than in the non-hip fracture group.The negative predictive values of previous fractures history, impaired vision, TUG and SWWT were higher than their positive predictive value.The specificities of previous fractures history, impaired vision, and SWWT were higher than their sensitivities.And the sensitivity of TUG was higher than its specificity. Conclusions:Hip fractures after stroke are common in elderly patients.Fractures often occur during daytime at home in daily activities.The previous fractures history, visual and cognitive dysfunction and impaired functional mobility are risk factors for hip fractures.We should take measures to prevent falls according to the relevant factors.Among the test scales, the timed up & go(TUG)scale could much more accurately identify patients at high risk for hip fractures.