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.

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.

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.

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 analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To study the epidemic status about genotype of the astrovirus, and to provide the epidemic data and control epidemic of infectious disease.Methods:Screening for astrovirus positive nucleic acids was performed using an astrovirus real-time fluorescent PCR kit. RT-PCR amplification was performed with astrovirus-specific primers Mn289/270. The positive products were recovered and purified and directly sequenced. Sequence analysis and phylogenetic analysis of astrovirus sequences were performed using Clustal and MEGA3.0 biological software.Results:From 2016 to 2018, we collected 496 fecal specimens from children with diarrhea from different regions, of them 136 cases had viral diarrhea, and in 17 of them astrovirus (3.4%) was detected, there were more males than females. All the 17 cases were under 5 years of age, and 12 cases (70.58%) were younger than 1 year old. In regional distribution, samples from Xining accounted for 64.70% (11/17), Huangzhong county for 29.41% (5/17), Huangnan Prefecture for 5.88%(1/17). The positive cases were mainly found in April to June, and there was another peak from October to December, which was consistent with the time distribution of rotavirus in past years. Seven strains were HAstV-1, one strain was HAstV-2, and the homology among four strains of HAstV-1 was 99.0%-100%. The homology with the other two strains of the same type was 88.4-95.7%.Conclusions:The dominant genotype of Astrovirus was HAstV-1 in infants with diarrhea in Qinghai, meanwhile there was also HAstV-2.

Objective:To understand the prevalence and genotype characteristics of enterovirus and Coxsackie virus in hand, foot and mouth disease (HFMD) patients in Qinghai province from 2015 to 2018.Methods:The throat swabs of HFMD patients were collected for virus isolation and RT-PCR in Qinghai province. The nucleotide sequence of the amplified products was determined and analyzed, and the gene evolution tree was constructed with reference to the sequence of some strains of NCBI.Results:From 2015 to 2018, 1 738 samples of clinical diagnosis positive cases were collected, including 326 EV-A71 cases, accounting for 18.76%, 237 CV-A16 cases, accounting for 13.64%, 628 CV-A6 cases, accounting for 36.13%. There were statistically significant differences among different genotypes in 4 years (EV-A71, χ2=245.315, P<0.001; CV-A16, χ2=27.680, P<0.001; CV-A6, χ2=702.713, P<0.001). A total of 317 cell culture isolates were obtained after isolation with RD cells. After sequence, DNA sequences of typical genotypes were selected for sequence analysis, from 2017 to 2018. The homology of all genotypes of VP1 was between 59% and 100%, the homology was 93% to 100% in 19 strains of EV-A71, the homology was 92% to 100% in 20 strains of CV-A16, the homology was 97% to 99% in 6 strains of CV-A6. According to the evolutionary tree, the sequences of EV-A71 strains are all on the C4a branch of the evolutionary tree in Qinghai province; 18 strains of CV-A16 were B1b and 2 stains were 1D; 5 strains of CV-A6 were D3 and 1 was B1. Conclusions:From 2015 to 2018, the prevalent genotypes of HFMD shifted from EV-A71 to CV-A16 and CV-A6 in Qinghai province, The EV-A71 genotype in Qinghai province has always been C4a genotype. There are different genotypes of CV-A16 and CV-A6. The nucleotide sequence differences between different genotypes are large, and the sequence variation among the same gene is small.

【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.