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.

Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

Bruton's tyrosine kinase(BTK)inhibitors are novel drugs targeted for the treatment of B-cell lymphoma.BTK inhibitors have pro-duced strong curative effects,especially for mantle cell lymphoma(MCL),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SSL),and Waldenstr?m's macroglobulinemia(WM).However,the adverse effect of bleeding has gradually been noted with the wide-spread use of BTK inhibitors in clinical practice.Bleeding events are caused by the off-target effects of BTK inhibitors,which affect platelet function through multiple signaling pathways during use.Bleeding affects patient treatment and threatens their quality of life.As such,the clinical management of bleeding should be strengthened.This paper provides a review of the mechanisms of action and clinical manage-ment of bleeding caused by BTK inhibitors.

Objective:To investigate the guiding significance of monitoring of immune factors and T lymphocyte subsets in immunomodulatory treatment of sepsis.Methods:Eighty patients with sepsis admitted to Nangyang First People's Hospital from June 2022 to December 2023 were selected as sepsis group,and 80 healthy volunteers who underwent physical examination during the same period were selected as health group.Detection of immune factors[complement C3,IgA,IgG,IgM,IFN-γ,programmed cell death receptor-1(PD-1)]and T lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)on the day of physical examination in healthy group,the day after sepsis group was enrolled,before treatment,and on day 1,3,and 7 after treatment,expressions of immune factors and T lymphocyte subsets were compared between the two groups.All 80 patients with sepsis received comprehensive treatment,during which thymosine-α1 was added for immunoconditioning treatment.Patients were divided into groups according to the improvement of their condition after immunoconditioning treatment[low-risk group(n=31),medium-risk group(n=34),high-risk group(n=15)]and disease outcome[survival group(n=55)and death group(n=25)].To analyze the efficacy of immune factors and T lymphocyte subsets in predicting the condition improvement and disease outcome of patients with sepsis after immune conditioning treatment.Results:Compared with healthy group,expression levels of immune factor complements C3,IgA,IgG,IgM and IFN-γ in sepsis group were decreased,relative expression level of PD-1 mRNA was increased,the values of CD4+T and CD4+T/CD8+T of T lymphocyte subsets were decreased,while CD8+T was increased(P<0.05).Compared with before treatment and 1 day after treatment,expression levels of complements C3,IgA,IgG,IgM,IFN-γ,CD4+T and CD4+T/CD8+T of T lymphocyte subsets were significantly increased in patients with sepsis after treatment on 3 and 7 days,while the relative expression level of PD-1 mRNA and CD8+T were significantly decreased(P<0.05).Condition of sepsis patients improved significantly after immune conditioning treatment,that is,proportion of low-risk patients increased,and proportion of medium-risk patients and high-risk patients decreased(Z=6.954,P<0.05).Levels of C3,IgA,IgG,IgM,IFN-γ,CD4+T and CD4+T/CD8+T in high-risk groups were significantly decreased,while PD-1 and CD8+T were significantly increased in low-risk and medium-risk groups(P<0.05).Levels of C3,IgA,IgG,IgM,IFN-γ,CD4+T and CD4+T/CD8+T in death group were significantly lower than those in survival group,while PD-1 and CD8+were significantly increased(P<0.05).ROC curve analysis showed that AUC of the combination of immune factors and T lymphocyte subsets to predict the improve-ment of the condition of sepsis patients after immune conditioning treatment was 0.923,the sensitivity was 89.90%,and the specificity was 82.31%.The efficacy of predicting the disease outcome of sepsis patients after immune conditioning treatment showed that the pre-dicted AUC was 0.965.The sensitivity was 95.60%and the specificity was 86.57%,which were obviously better than the single item.Conclusion:Sepsis patients have immune dysfunction related to immune factors and abnormal T lymphocyte subsets,immunomodu-latory therapy can help improve immune dysfunction,monitor immune factors upon admission,and levels of T lymphocyte subsets are helpful for early prediction of disease progression and prognosis in sepsis patients after immunomodulatory therapy.

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC₅₀) values of 3.22, 4.78, 8.90, and 4.31 μmol·L^-1, respectively.
Mice ; Animals ; Coumarins/chemistry* ; Rutaceae/chemistry* ; Anti-Inflammatory Agents/pharmacology* ; Plant Extracts/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure

【Objective】 To investigate the association of platelet/albumin ratio （PAR）， platelet/hemoglobin （PHR） and C-reactive protein/albumin （CAR） with diabetes mellitus. 【Methods】 Based on the data of China Health and Nutrition Survey （CHNS2009）， with gender and age matched by their ID， a total of 8 258 individuals with serological test results were finally included and were divided into diabetes group and control group according to the fasting blood glucose and HbA1c， and then the blood lipid and blood cell changes， PAR， PHR and CAR differences between groups were compared， and the correlation analysis of diabetes was performed. 【Results】 Compared with those in the control group， serum uric acid， total cholesterol， triacylglycerol and low-density lipoprotein cholesterol （LDL-C） were significantly increased in diabetes group， while high-density lipoprotein cholesterol （HDL-C） was significantly decreased. Besides， there was no significant difference in PAR or PHR between the two groups， while CAR was significantly increased in diabetes （0.48±0.18 vs. 0.08±0.23， P<0.001）， and was positively correlated with the levels of fasting glucose （r=0.181 8， P<0.001）， HbA1c （r=0.186 6， P<0.001）， and HOMA-IR （r=0.188 1， P=0.003）. However， CAR was not an independent risk factor for diabetes. In addition， increased red blood cell count （B=1.324， 95% CI： 1.182-1.483， P<0.001） and leukocytes count （B=1.230， 95% CI： 1.166-1.298， P<0.001） may be independent risk factors for the incidence of diabetes. 【Conclusion】 CAR is correlated with diabetes mellitus， but it is not an independent risk factor. Dyslipidemia， elevated leukocytes and red blood cell counts may be independent risk factors for diabetes， but further study is needed.

【Objective】 To explore the correlation of the intake of different nutrients with the levels of serum lipids and uric acid. 【Methods】 Based on the data of China Health and Nutrition Survey （CHNS2009）， a total of 1 343 individuals were finally included by ID matching with demographic data， serological tests and dietary nutrition results. We compared serum lipids and uric acid levels between groups of different nutrients intake （group Q1-Q4） and conducted the correlation analysis. 【Results】 The total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL-C） in the men were significantly higher than those in the women， while high-density lipoprotein （HDL-C） was significantly lower in the men. The average intakes of daily energy， carbohydrate， fat and protein were significantly higher in the males than in the females. Intergroup comparisons and correlation analyses showed that total energy and protein intakes were positively correlated with TG （r=0.070 9，P=0.008 4；r=0.051 7，P=0.012 3）， while fat intake was positively correlated with TC （r=0.086 1，P=0.001 4）. The blood uric acid level was positively correlated with the intake of fat and protein （r=0.127 3，P<0.001；r=0.138 0，P<0.001）. The results of subgroup analysis of the males were consistent with those of the whole population. However， there was a significantly negative correlation between carbohydrate intake and blood uric acid level in the females （r=-0.107 9，P＝0.002 2）. Multiple linear regression analysis showed that TC， TG and uric acid were correlated with gender， age and intake of different nutrients. 【Conclusion】 The levels of blood uric acid and lipids are significantly higher in men than in women. Different types of dyslipidemia and hyperuricemia are related to different nutrient intakes in different genders and ages.

【Objective】 To explore the potential mechanism of Salvia miltiorrhiza and its active monomers in patients with coronary heart disease （CHD） complicated with depression or anxiety disorder based on network pharmacology. 【Methods】 We collected the clinical data of 147 patients with CHD admitted to our hospital from March to April 2021 and investigated biochemical examination， drug treatment and the use of Chinese herbal compound. The downstream targets of active monomers of Salvia miltiorrhiza were screened based on TCMSP， PubChem and SwissTargetPrediction databases， and depression or anxiety-related genes were mining in OMIM， GeneCards and TTD databases. Protein-protein interaction network and GO and KEGG gene enrichment analyses were performed by matching Chinese herbal compound with disease targets. Chinese herbal compound-target-disease network was built by Cytoscape. 【Results】 Shuxuening （44.9%）， Salviae miltiorrhiza （27.9%）， and Sofren injection （21.8%） were the most commonly used Chinese herbal or injections in the clinical treatment of CHD， and there was no difference in the frequency of use between genders. Network pharmacology showed that the active components of Salvia miltiorrhiza might act on neuroactive ligand-receptor binding， 5-hydroxytryptamine synapses and dopaminergic synapses and participate in the regulation of neurotransmitter transport， dopamine and catecholamine metabolism and stress response. Target-disease network analysis showed that many active components of Salvia miltiorrhiza interacted with catechol-O-methyltransferase， monoamine oxidase， 5-hydroxytryptamine receptor and opioid receptor， which may be the potential targets of Salvia miltiorrhiza in improving depression and anxiety. 【Conclusion】 Salvia miltiorrhiza is involved in the regulation of neurotransmitters and synaptic activities， thus making it a potential drug for the clinical treatment of CHD complicated with depression and anxiety disorder.

【Objective】 To investigate the inhibitory effect of magnesium citrate （MgCit） on hyperphosphorus-induced VSMCs calcification and its mechanisms. 【Methods】 VSMCs were divided into the following groups： normal control group， high-phosphorus group， low-dose MgCit group， high-dose MgCit group and high-dose MgCit+NPS2143 （calcium-sensitive receptor inhibitor） group. Alizarin red staining was used for semi-quantitative analysis of VSMCs calcification and the calcium content in VSMCs was detected by the commercial kit. The osteogenic transdifferentiation parameters including alkaline phosphatase （ALP） activity， as well as mRNA and protein levels of smooth muscle 22α （SM22α）， runt-related transcription factor 2 （RUNX2） and bone morphogenetic protein 2 （BMP2）， were detected in each group. 【Results】 Compared with those in the control group， the calcium content of VSMCs in the model group was increased， ALP activity， and the mRNA and protein expressions of RUNX2 and BMP2 were increased， and the mRNA expression of SM22α was decreased （P<0.05）. MgCit could reduce VSMCs calcification， decrease ALP activity， decrease mRNA and protein levels of RUNX2 and BMP2， and increase mRNA levels of SM22α induced by high-phosphorous （P<0.05）. The above effects of MgCit were reduced when NPS2143 was administered simultaneously （P<0.05）. 【Conclusion】 MgCit can reduce VSMCs calcification and osteogenic transdifferentiation induced by high phosphorus through activating of CaSR.