Objective To construct a nomogram model for predicting the risk of in-hospital death in CHF patients by using noninvasive hemodynamic monitoring combined with age,DBP,CRP and renal insufficiency(serum creatinine≥ 442 μmol/L).Methods A total of 223 elderly patients with acute onset of CHF admitted in First,Second Medical Centre of Chinese PLA General Hos-pital from September 2022 to March 2023 were recruited in this study.According to their clinical outcomes,they were divided into survival group(196 cases)and death group(27 cases).Based on the in-hospital death and other related indicators,a nomogram model was constructed to predict the risk factors of in-hospital death in CHF.Results Noninvasive hemodynamic mornitoring indi-cated that the death group had significantly higher LVEF and LCWI values but lower LVEDV value than the survival group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age(OR=1.131,95％CI:1.052-1.213,P=0.001),DBP(OR=0.932,95％CI:0.882-0.982,P=0.011),CRP(OR=1.171,95％CI:1.021-1.352,P=0.024),LVEDV(OR=0.984,95％CI:0.962-0.992,P=0.011)and renal insufficiency(OR=5.863,95％CI:1.351-1.731,P=0.004)were independent risk factors for the short-term prognosis of the elderly CHF patients.The AUC value of the nomogram model was 0.902(95％CI:0.819-0.948,P＜0.05),and calibration curve analysis showed the C-index was 0.902,indicating accurate predictive perform-ance.Conclusion Age,DBP,LVEDV,CRP and renal insufficiency are independent risk factors for the short-term prognosis of the elderly CHF patients.

The Chinese Neonatal Network(CHNN) was established in 2018 with the mission of establishing a national collaboration platform, conducting high-quality and collaborative research, and ultimately improving the quality of neonatal-perinatal care and health in China.At present, 112 hospitals across the country have joined CHNN.CHNN has established a national standardized cohort of very premature infants/very low birth weight infants with >10 000 enrollments each year, has been leading data-driven collaborative quality improvement initiatives, conducting multicenter clinical studies, and performing multi-level training programs.Guided by the principles of collaboration and sharing, data-driven, continuous improvement, and international integration, CHNN has become an important platform for clinical and research collaboration in neonatal medicine in China.

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99％of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

L-theanine has been shown to have a therapeutic effect on depression.However,whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained.Given the complexity of the pathogenesis of depression,this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies.Behavioral tests,hippocampal tissue sections,and serum and hippocampal biochemical indexes were studied,and the results confirmed the preventive effect of L-theanine.Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spec-trometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spec-trometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment.The results suggested that 28 abnormal me-tabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration.These biomarkers were involved in various metabolic pathways,mainly including amino acid metabolism and lipid metabolism.The levels of amino acids and neurotransmitters in the phenylalanine,tryptophan,and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats.In summary,L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body,such as amino acids,lipids,and inflammation.This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.

Humans ; Myocardial Infarction/surgery* ; Bone Marrow Transplantation ; Bone Marrow Cells ; Ventricular Function, Left

OBJECTIVE: To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD). METHODS: Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation Surveyor^TM software. RESULTS: The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature. CONCLUSION This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".
Female ; Humans ; Afibrinogenemia/congenital* ; East Asian People ; Fibrinogen/genetics* ; Mothers ; Mutation ; Pedigree

Objective:To compare the clinical efficacy and safety of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for patients with advanced gastric cancer.Methods:A total of 52 patients with human epidermal growth factor receptor 2 (HER2) negative and inoperable locally advanced or advanced gastric cancer who were pathologically diagnosed from January 2018 to January 2021 in the Second Affiliated Hospital of Shandong First Medical University were collected. The patients were divided into continuous dosing group and alternate-day dosing group by random number table method. The continuous dosing group received apatinib (250 mg, once a day) combined with SOX regimen (S-1+oxaliplatin); the alternate-day dosing group received apatinib (250 mg, once every other day) combined with SOX regimen. Twenty-one days were a cycle, and the efficacy was evaluated after 2 cycles. After 4-6 cycles, patients with stable disease received apatinib and S-1 for maintenance therapy. The therapeutic effects and adverse reactions of the two groups were compared.Results:The curative effect could be evaluated in 51 patients, including 26 in the continuous dosing group and 25 in the alternate-day dosing group. The disease control rates in the continuous dosing group and the alternate-day dosing group were 84.6% (22/26) and 76.0% (19/25) ( χ2 = 0.60, P = 0.499), and the median progression-free survival time was 7.50 months (95% CI 6.17-8.83 months) and 8.30 months (95% CI 6.99-9.61 months) ( χ2 = 0.71, P = 0.401), and the median overall survival time was 15.50 months (95% CI 11.30-19.69 months) and 15.60 months (95% CI 13.63-17.57 months) ( χ2 = 1.82, P = 0.177). The main adverse reactions in the two groups were leukopenia, thrombocytopenia, hypertension, nausea, vomiting, fatigue, hand-foot syndrome, proteinuria, liver and kidney damage. The incidence rates of ≥grade 3 adverse reactions in the continuous dosing group and the alternate-day dosing group were 42.3% (11/26) and 12.0% (3/25), and the difference was statistically significant ( χ2 = 4.46, P = 0.035). Conclusions:The efficacy of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for advanced gastric cancer is similar, but the incidence of ≥grade 3 adverse reactions in alternate-day dosing group is lower, which improves the compliance and tolerance of patients.

Objective:To observe the clinical characteristics and guideline compliance of chronic obstructive pulmonary disease (COPD) patients with initial triple therapy in real-life world.Methods:This study is a cross-sectional study. The subjects of the study were COPD patients admitted to 13 hospitals in Hunan Province and Guangxi Zhuang Autonomous Region from December 2016 to December 2021. The initial treatment was triple inhaled drugs. The data collected included gender, age, diagnosis, body mass index (BMI), history of acute exacerbation (AE) in the past year, pulmonary function, COPD Assessment Test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC), inhaled drugs and other indicators. The characteristics and differences of COPD patients before and after 2020 were analyzed.Results:7 184 patients with COPD were enrolled in this study, including 2 409 COPD patients treated with initial triple therapy, accounting for 33.5%(2 409/7 184). Taking January 1st, 2020 as the cut-off point, 1 825 COPD patients (75.8%) received initial treatment with triple inhaled drugs before 2020 and 584 patients (24.2%) after 2020 were included in this study. Compared with COPD patients before 2020, the COPD patients after 2020 had higher FEV 1% [(40.9±15.5 )% vs (39.3±15.5)%, P=0.040], lower CAT [(15.8±6.5)point vs (17.5±6.2)point, P<0.001], less AE in the past year [1(0, 2)times vs 1(0, 2)times, P=0.001] and higher rate of non-AE [255(43.7%) vs 581(37.1%), P=0.006]. In addition, before 2020, patients with COPD were mainly treated with open triple drugs (1 825/1 825, 100%); after 2020, 306 patients (52.4%) received open triple inhaled drugs, and 278 patients (47.6%) received closed triple inhaled drugs. Conclusions:In real-life world, most of patients with COPD treated with triple therapy have severe lung function, obvious symptoms and high risk of acute exacerbation. The real-world prescribing of triple therapy in patients with COPD does not always reflect recommendations in guidelines and strategies, and overtreatment is common. After 2020, prescribing triple therapy for COPD patients is more positive and worse consistency with guideline.

Objective:To study the Epstein-Barr virus (EBV) activity and its clinical characteristics in patients with hemorrhagic fever with renal syndrome (HFRS). Methods:From January 2016 to August 2017, patients with HFRS who were hospitalized in the First Affiliated Hospital of Harbin Medical University were routinely tested by EBV serology, and were divided into two groups according to their presence or absence of EBV infection, namely EBV active group and non-EBV active group. The clinical data between the two groups were compared and analyzed by SPSS 18.0.Results:A total of 188 HFRS patients were enrolled, including 73 cases in EBV active group and 115 cases in non-EBV active group. The EBV active rate of HFRS patients was 38.83% (73/188). The incidences of lumbago [57.53% (42/73) vs 42.61% (49/115)], abdominal pain [42.47% (31/73) vs 20.00% (23/115)], skin and mucosa congestion [57.53% (42/73) vs 39.13% (45/115)], and conjunctiva edema [50.68% (37/73) vs 28.70% (33/115)] in EBV active group were significantly higher than those in non-EBV active group (χ 2 = 3.983, 11.008, 6.083, 9.239, P < 0.05). There were 10, 7 and 43 patients with acute kidney injury (AKI) stage 1, 2 and 3 in EBV active group and 5, 13 and 53 patients in non-EBV active group. Degree of AKI in EBV active group was higher than that in non-EBV active group, and the difference was statistically significant (χ 2 = 12.615, P < 0.05). In EBV active group, the proportion of patients whose renal function recovery over 15 days [23.29% (17/73)] and white blood cell count [11.26 (3.39 ~ 54.23) × 10 9/L] were significantly higher than those in non-EBV active group [6.96% (8/115), 10.03 (2.91 ~ 66.99) × 10 9/L], and the differences were statistically significant (χ 2 = 10.330, Z = - 2.003, P < 0.05). Conclusion:HFRS patients may cause latent EBV activity, complicate their clinical features, cause severe renal damage and prolong the recovery time of renal function.

OBJECTIVE：To provide reference for the identification and proces sing end-point determination of raw Morus alba and its processed products （honey-processed M. alba ）. METHODS ：UPLC method was adopted. The determination was performed on Waters BEH Shield RP C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid solution （gradient elution ） at the flow rate of 0.30 mL/min. The column temperature was set at 30 ℃. The program wavelengths were set at 280 nm（0-4 min） and 320 nm（4-35 min）. Similarity Evaluation System for Chromatogram Fingerprint of TCM （2012 edition）was used to establish UPLC fingerprint and carry out similarity evaluation of 13 batches of M. alba and honey-processed M. alba . The chromatographic peaks were identified with reference substance fingerprint. The colorimetric value （L，a，b） of 13 batches of M. alba and honey-processed M. alba powder were determined ，and average total colorimetric value （E）was calculated. OPLS-DA and cluster analysis were adopted to analyze the differences in fingerprints and colorimetric values of M. alba before and after processing. At the same time ，the dynamic change rule of fingerprint and colorimetric value of honey-processed M. alba at different processing time points were analyzed to determine the processing end-point. RESULTS ：There were obvious differences in fingerprints before and after processing ，and the similarity of 13 batches of M. alba and honey-processed M. alba were all higher than 0.9. Totally 21 common peaks were calibrated for M. alba ，and 23 common peaks for honey-processed M. alba ；peak 1 and peak 2 were newly produced compounds of honey-processed M. alba . Peak 2，peak 7，peak 14 and peak 19 were identified as 5-hydroxymethylfurfural， mulberry glucoside A ，oxidized resveratrol ，mulberry flavonoids G. Results of OPLS-DA showed that the peak area-sample quantity ratio of peak 1，peak 2，peak 18，peak 20 and the chromaticity values （L，a，b）were the most important factors affecting the difference of raw and processed products of M. alba . When the E ranged 75.84-80.88 as the processing end-point of honey-processed M. alba ，the processing time was determined as 22-34 min. CONCLUSIONS ： The established UPLC fingerprint and colorimetric value determination method can be used to identify the raw and processed products of M. alba as well as determine the processing end-point of honey-processed M. alba .