Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective:To explore the genetic basis for a child featuring global developmental delay and epilepsy.Methods:A child who had presented at Guangzhou Women and Children′s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c. 115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+ PM3_Supporting+ PP3_Moderate+ PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. Conclusion:The homozygous c. 115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

Objective:To investigate the therapeutic effect of comprehensive geriatric assessment(CGA) in elderly patients with chronic heart failure(CHF) complicated with sarcopenia, and to provide a theoretical reference for clinical application.Methods:This study was a prospective randomized controlled study. 110 elderly CHF patients with myopenia admitted to the Third People's Hospital of Hefei from January 2019 to February 2022 were selected. Using the random number table method, 56 cases were divided into an observation group and 54 cases into a control group. Before treatment, the control group of patients underwent a selective single assessment based on the hospital's requirements and the patient's actual situation, including a fall risk assessment, nutritional risk screening checklist assessment, and routine medication to improve cardiac function and prognosis; Before treatment, the patients in the observation group were assessed with CGA, including the assessment of physical function, mental and psychological status, multiple drug management, pain, Sleep disorder, and social environment. According to the assessment results, individual diagnosis and treatment plans were formulated, implemented, and dynamically adjusted. The two groups were treated for 12 weeks. The general information, treatment compliance, B-type brain natriuretic peptide (BNP) level, left ventricular Ejection fraction (LVEF), 6 min walking distance (6MWD), arm strength of upper limbs and 6 m walking speed, clinical efficacy and prognosis of the two groups were compared before and after treatment. The measurement data is represented by xˉ± s, group t-tests are used for inter group comparison, and paired t-tests are used for intra group comparison before and after treatment; Counting data is represented as an example (%), and inter group comparisons are made using χ 2 test, non parametric rank sum test was used for inter group comparison of hierarchical data. Results:There was no statistically significant difference in gender, age, course of CHF, smoking, alcohol consumption, number of comorbidities, cardiac function grading, and treatment compliance between the two groups of patients (all P>0.05), indicating comparability. Before treatment, there was no statistically significant difference in plasma BNP, LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed between the two groups of patients (all P>0.05); After treatment, the BNP of both groups of patients was lower than before treatment and the observation group was lower than the control group. LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed were all higher than before treatment and the observation group was higher than the control group [(343.45±34.95) ng/L vs (387.09±46.96) ng/L, (49.61±7.11)% vs (42.94±5.72)%, (348.92±37.73) m vs (297.74±43.48) m, (22.64±3.82) kg vs (19.48±3.88) kg, (0.97±0.10) m/s vs (0.83±0.12) m/s], The differences were statistically significant ( t-values were 5.51, -5.40, -6.60, -4.31, -6.60, all P<0.001). After 12 weeks of treatment, there was no statistically significant difference in clinical efficacy between the two groups of patients ( P=0.216), but the overall poor prognosis rate in the follow-up observation group was lower than that in the control group [7.14%(4/56) vs 22.22% (12/54)], and the difference was statistically significant (χ 2=5.03, P=0.025). Conclusions:Developing, implementing, and dynamically adjusting the individualized treatment plan involving CGA can improve the prognosis of elderly CHF patients with sarcopenia, help improve cardiac function, increase grip strength and somatic function, and reduce the risk of major adverse cardiovascular events ,all-cause mortality in elderly patients with CHF combined with sarcopeni and has certain clinical application value.

Objective:To explore the diagnosis and treatment of pure red cell aplastic anemia (PRCA) caused by parvovirus B19 (HPV-B19)infection after liver transplantation (LT).Methods:Three adult PRCA patients caused by parvovirus B19 infection after LT were reviewed retrospectively.The relevant literatures were collected to sort out the detection methods and treatment of parvovirus B19 infection after LT.Results:All three patients received liver transplantation due to end-stage liver disease with massive intraoperative blood transfusion and smooth postoperative recovery.Severe anemia occurred at 1-2 Months after discharge.Hemorrhagic anemia was excluded after re-admission and PRCA was diagnosed by bone marrow aspiration and next generation sequencing (NGS). After tapering the intensity of immunosuppressive therapy, intravenous immunoglobulin (IVIG) was administered for 7-10 days and hemoglobin soon normalized.A review of 15 recent literatures on HPV-B19 infection after LT revealed that the diagnosis and treatment of parvovirus B19 infection after LT gradually were became same.Conclusions:HPV-B19 infection causes PRCA after LT in adults.Diagnosing with NGS, intravenous injection of immunoglobulin and modification of immunosuppressant regimen may achieve excellent therapeutic efficacies.

Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling pathway may play important roles in a variety of neurological diseases, particularly in the development and treatment of epilepsy. The BDNF gene and NTRK2 gene are genes encoding BDNF and TrkB proteins in this pathway. The variations in these two genes may affect the occurrence and treatment of epilepsy through leading to abnormal functions and expressions of the encoded proteins, which may affect the degrees of activation of BDNF-TrkB signaling pathway. This article summarizes the pathophysiological processes of epilepsy in which BDNF-TrkB signaling pathway genes and their encoded proteins may be involved.

Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride to provide experimental basis for the development of new preparations.Methods:The concentration of nebivolol hydrochloride was determined by an HPLC method,and a saturated solution method and a shake-flask method were respectively applied to determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride in water,0.1 mol·L-1 HCl solution and phosphate buffer solution with different pH values(pH2.0,pH6.8,pH7.4 and pH8.0).Results:At (37±0.5)℃,the equilibrium solubility of nebivolol hydrochloride in water and in 0.1 mol·L-1 HCl solution was 722.53 μg·ml-1and 56.07μg·ml-1,respectively.The apparent oil/water partition coefficient (Log P) of nebivolol hydrochloride was 1.17 and 1.32,respectively.Within the pH range of 2.0-7.4,with the increase of pH value, the equilibrium solubility and the Log P decreased and increased,respectively,while pH value increased from 7.4 to 8.0,the equilibrium solubility of nebivolol hydrochloride increased and Log P decreased.Conclusion:The method is accurate and reliable.Nebivolol hydrochloride has poor water solubility,and the equilibrium solubility and the Log P are both influenced by pH values.

To investigate the effect of RAD18-siRNA on cell proliferation and chemotherapy sensitivity of esophageal squamous cell carcinoma (ESCC) ECA-109 cells.RAD18-siRNA was transfected into human ECA-109 cells by Lipofectamine 3000. Quantitative PCR and Western blot were performed to detect RAD18 and CyclinD1 expression; CCK-8 assay was used to determine cell proliferation and chemotherapy drug sensitivity; flow cytometry was used to determine cell cycle. Correlation between RAD18 and CyclinD1 mRNA expression was analyzed by Pearson's correlation.Compared with non-transfected cells, the expression of RAD18 in RAD18-siRNA group was significantly decreased (<0.05). The cell proliferation was inhibited (<0.05) and the cell number of G1 phase was increased, G2/M phase cells decreased (<0.05) in RAD18-siRNA group. After treatment with different concentrations of cisplatin or 5-FU, the survival rate of the two cell groups was reduced (all<0.05), and the IC50 of RAD18-siRNA group was significantly lower than that of non-transfected group (<0.05). The mRNA expression of RAD18 was positively correlated with CyclinD1 expression in ESCC tissues(=0.478,<0.01).Down-regulated expression of RAD18 can decrease the cell proliferation and increase chemo-sensitivity of ESCC cells, and CyclinD1 may participate in the process.
Adjuvants, Pharmaceutic ; pharmacology ; Carcinoma, Squamous Cell ; drug therapy ; physiopathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Cyclin D1 ; drug effects ; genetics ; DNA-Binding Proteins ; administration & dosage ; pharmacology ; Down-Regulation ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Drug Synergism ; Esophageal Neoplasms ; drug therapy ; physiopathology ; Fluorouracil ; pharmacology ; G1 Phase ; drug effects ; G2 Phase ; drug effects ; Humans ; Metaphase ; drug effects ; RNA, Small Interfering ; administration & dosage ; pharmacology ; Transfection ; Ubiquitin-Protein Ligases ; administration & dosage ; pharmacology

Objective To assess the value of spectral CT in differentiating benign and malignant serous cavity effusion in vitro.Methods 41 plastic tubes filled with serous cavity effusion underwent spectral CT imaging.The gemstone spectral imaging(GSI)viewer was used to measure the mean CT values of water -iodine concentration, iodine -water concentration,monochromatic images(40 -140KeV,interval of 5KeV),140KVp QC,and EFF -Z. Slope of spectral curve was measured also.Based on clinical and pathological diagnosis,30 cases of benign and 11 cases of malignant serous cavity effusion were compared.The difference of the spectral characteristic parameters was evaluated statistically by independent -samples t test using SPSS 18.0.Results The EFF -Z,water -iodine concentration,iodine -water concentration,and slope of spectral curve[7.26 ±0.25,(1 021.82 ±6.37)mg/mL, (-3.23 ±1.53)mg/mL,0.26 ±0.12]of benign serous cavity effusion showed no statistically significant differences between the malignant group[7.31 ±0.10,(1 016.17 ±5.32)mg/mL,(-3.06 ±1.18)mg/mL,(0.24 ±0.10), t =0.652,2.016,0.332,0.482,all P >0.05 ].There were statistically significant differences on 55 -140 KeV between the two groups[(4.87 ±7.13)and (10.66 ±6.70),(7.17 ±6.48)and (12.71 ±5.94),(9.58 ±6.11) and (14.96 ±5.65),(11.63 ±5.97)and (16.77 ±5.52),(13.31 ±5.93)and (18.36 ±5.52),(14.66 ± 5.98)and (19.52 ±5.52),(16.06 ±6.06)and (20.90 ±5.63),(17.03 ±6.10)and (21.42 ±5.88), (17.58 ±6.12)and (22.29 ±5.59),(18.05 ±6.14)and (22.74 ±5.49),(18.52 ±6.17)and (23.19 ± 5.51),(18.74 ±6.20)and (23.33 ±5.46),(19.16 ±6.20)and (23.80 ±5.47 ),(19.30 ±6.26 )and (23.87 ±5.45),(19.57 ±6.26)and (24.19 ±5.48),(19.66 ±6.28)and (24.21 ±5.43),(19.92 ±6.31) and (24.46 ±5.44),(20.00 ±6.32)and (24.53 ±5.43),t =2.339,2.474,2.544,2.489,2.456,2.356,2.301, 2.060,2.231,2.223,2.206,2.161,2.188,2.138,2.162,2.122,2.114,2.104,all P <0.05].However,there were no statistically significant differences on 40 -50 KeV[(-5.51 ±11.82)and (0.96 ±11.59),(-0.41 ±9.77) and (5.75 ±9.85),(2.47 ±8.21)and (8.19 ±8.11),t =1.559,1.785,1.984,all P >0.05].The difference be-tween benign and malignant effusion was statistically significant on 140KVp QC also [(10.25 ±6.96,16.60 ±6.84) (t =2.601,P =0.013)].Conclusion Some spectral CT characteristic parameters especially 55 -140 KeV mono-chromatic images can differentiate benign and malignant effusion.Spectral CT maybe afford a new method to differenti-ate benign and malignant effusion.