AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

Ovarian cancer （OC） is one of the most common malignant tumors in women， with the mortality rate being the highest among gynaecological malignant tumors. As the atypical symptoms of OC are difficult to be detected in the early stage， most patients are already in the advanced stage when being diagnosed. As a result， the clinical treatment has limited effects. Currently， the main therapies for OC are surgery and chemotherapy， while their drug resistance and adverse reactions seriously reduce the quality of life of patients. In recent years， traditional Chinese medicine （TCM） has attracted the attention of clinicians and researchers because of its high efficacy， low toxicity， and mild side effects. According to the TCM philosophy of treatment based on syndrome differentiation， the Chinese medicines with multiple targets， wide range， and mild side effects can be screened based on the molecular targets involved in the occurrence and development of OC， which can bring out the unique advantages of TCM in the treatment of OC. Modern studies have shown that the occurrence and development of OC are closely related to the abnormal expression of multiple signaling pathways. The continued abnormal activation of the signal transducer and activator of transcription 3 （STAT3） signaling pathway can lead to abnormal proliferation and malignancy of OC. cause abnormal proliferation and malignant transformation of OC， which is closely related to the development of OC. In addition， studies have shown that Chinese medicine can inhibit the proliferation， angiogenesis， invasion， and metastasis and promote the autophagy and apoptosis of OC cells by regulating the Janus kinase 2 （JAK2）/STAT3 signaling pathway， providing new therapeutic strategies and ideas for the prevention and treatment of OC. This paper summarizes the role of JAK2/STAT3 signaling pathway in OC development by reviewing the relevant articles and reviews the mechanism and research progress of active components and compound prescriptions of Chinese medicine intervening in OC development by regulating the JAK2/STAT3 signaling pathway. This review is expected to provide a systematic reference for clinical research and drug development of OC.

Objective:To analyze the safety profile of blinatumomab in children with B-cell acute lymphoblastic leukemia (ALL).Methods:Demographic and clinical data of 33 pediatric B-cell ALL patients treated with blinatumomab in the Women and Children′s Hospital, Qingdao University from January 2022 to November 2024 were retrospectively collected. Demographic data included gender and age, while clinical data comprised leukemia risk stratification, minimal residual disease (MRD) status before blinatumomab use, treatment duration (14-day or 28-day courses), and safety outcomes included drug-related fever, cytokine release syndrome (CRS), tachycardia, blood pressure abnormalities, elevated transaminases, immune effector cell-associated neurotoxicity syndrome (ICANS), oral mucositis, rash, and infections. Patients were stratified by CRS occurrence and transaminase elevation for comparative analysis of demographic/clinical characteristics.Results:A total of 33 children with B-cell type ALL who received blinatumomab treatment were included. Among them, 21 were male and 12 were female; the age was 5.2 (4.7, 7.0) years, ranging from 1.7 to 10.0 years. Risk stratification included low (2 cases), intermediate (23 cases), and high (8 cases) risk. Pre-treatment MRD was negative in 16 and positive in 17 patients. Eight patients received a 14-day blinatumomab course, while 25 cases received a 28-day course. The overall adverse events (AEs) rate was 81.8% (27/33). Among the 27 patients who experienced AEs, there were 5 cases (18.5%) of severe adverse events (all grade 3). The specific adverse events that occurred in the 33 patients included drug-related fever in 21 cases (63.6%) [including 16 cases (48.5%) of CRS], elevated transaminases in 10 cases (30.3%), infectious symptoms in 5 cases (15.2%), rash in 4 cases (12.1%), tachycardia in 3 cases (9.1%), ICANS in 2 cases (6.1%), and oral mucositis in 1 case (3.0%). No statistically significant differences were observed in gender, age, risk stratification, pretreatment MRD status, and treatment duration between the CRS and non-CRS groups, transaminase-elevated and normal groups (all P>0.05). Conclusions:In pediatric B-cell ALL, the most common AEs related to blinatumomab are CRS and elevated transaminases, but most reactions are mild, with rapid recovery and favorable tolerability.

Objective:To analyze the safety profile of blinatumomab in children with B-cell acute lymphoblastic leukemia (ALL).Methods:Demographic and clinical data of 33 pediatric B-cell ALL patients treated with blinatumomab in the Women and Children′s Hospital, Qingdao University from January 2022 to November 2024 were retrospectively collected. Demographic data included gender and age, while clinical data comprised leukemia risk stratification, minimal residual disease (MRD) status before blinatumomab use, treatment duration (14-day or 28-day courses), and safety outcomes included drug-related fever, cytokine release syndrome (CRS), tachycardia, blood pressure abnormalities, elevated transaminases, immune effector cell-associated neurotoxicity syndrome (ICANS), oral mucositis, rash, and infections. Patients were stratified by CRS occurrence and transaminase elevation for comparative analysis of demographic/clinical characteristics.Results:A total of 33 children with B-cell type ALL who received blinatumomab treatment were included. Among them, 21 were male and 12 were female; the age was 5.2 (4.7, 7.0) years, ranging from 1.7 to 10.0 years. Risk stratification included low (2 cases), intermediate (23 cases), and high (8 cases) risk. Pre-treatment MRD was negative in 16 and positive in 17 patients. Eight patients received a 14-day blinatumomab course, while 25 cases received a 28-day course. The overall adverse events (AEs) rate was 81.8% (27/33). Among the 27 patients who experienced AEs, there were 5 cases (18.5%) of severe adverse events (all grade 3). The specific adverse events that occurred in the 33 patients included drug-related fever in 21 cases (63.6%) [including 16 cases (48.5%) of CRS], elevated transaminases in 10 cases (30.3%), infectious symptoms in 5 cases (15.2%), rash in 4 cases (12.1%), tachycardia in 3 cases (9.1%), ICANS in 2 cases (6.1%), and oral mucositis in 1 case (3.0%). No statistically significant differences were observed in gender, age, risk stratification, pretreatment MRD status, and treatment duration between the CRS and non-CRS groups, transaminase-elevated and normal groups (all P>0.05). Conclusions:In pediatric B-cell ALL, the most common AEs related to blinatumomab are CRS and elevated transaminases, but most reactions are mild, with rapid recovery and favorable tolerability.

Objective To study the changes in serum autophagy markers in children with retinopathy of prematurity(ROP)and its clinical value.Methods Premature infants who were screened for ROP in our hospital from January 2020 to December 2022 were selected as the study subjects.Those screened out with ROP at 4-6 weeks of birth were assigned to the ROP group and those without ROP to the control group.The levels of serum autophagy markers LC3-Ⅱ,Beclin-1 and P62 were detected at the 3rd day,1st,2nd and 3rd weeks of birth.The two groups were compared in terms of serum autophagy markers.The diagnostic efficacy of serum autophagy markers on ROP was analyzed.Results There was no significant difference in serum LC3-Ⅱ,Beclin-1 and P62 levels between the ROP group and control group at the 3rd day of birth(P>0.05).At the first,second and third weeks of birth,how-ever,the ROP group showed significantly lower levels of serum LC3-Ⅱ and Beclin-1 but higher level of P62 com-pared to the control group(both P<0.05).The levels of serum LC3-Ⅱ,Beclin-1 and P62 at the first,second and third weeks of birth had diagnostic value for ROP.The children in the ROP group who did not receive mechanical ventilation and oxygen inhalation,and did not develop with sepsis and bronchopulmonary dysplasia showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the first,second and third weeks of birth compared to those without the above-mentioned treatment as well as those complications(all P<0.05).In the ROP group,those with severe ROP showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the 3rd day,and 1st,2nd and 3rd week of birth(all P<0.05).Conclusion The levels of serum autophagy markers in children with ROP show significant changes since the first week of birth,so they have diagnostic efficacy for the diseases.

Objective: To construct a prediction model for preeclampsia (PE) risk in twin-pregnant women, so as to provide the basis for early screening and prevention of PE. Methods: A total of 467 twin-pregnant women who underwent prenatal examination and delivered at Huzhou Maternal and Child Health Hospital were selected. Sixty cases with preeclampsia (PE) were included in the case group, and 60 women without PE were included in the control group. General information, blood biochemical indicators and uterine artery resistance index (UtA-RI) were collected. A logistic regression model was used to screen predictive factors and establish a nomogram. The Bootstrap method was performed for the internal validation; the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: In the case group, there were 47 individuals (78.33%) aged younger than 35 years, 21 individuals (35.00%) with pre-pregnancy body mass index (BMI) of 25 kg/m2 and above, and 33 individuals (55.00%) with in vitro fertilization. In the control group, there were 57 individuals (95.00%) aged younger than 35 years, 8 individuals (13.33%) with pre-pregnancy BMI of 25 kg/m2 and above, and 39 individuals (65.00%) with natural pregnancy. Multivariable logistic regression analysis identified age, pre-pregnancy BMI, method of conception, placental growth factor (PLGF) and UtA-RI as risk prediction factors for PE in twin-pregnant women. The established nomogram had an area under the ROC curve of 0.827 (95%CI: 0.755-0.899), a sensitivity of 0.767, a specificity of 0.733, a good discrimination and calibration, and a relatively high clinical net benefit. Conclusion The nomogram established by age, pre-pregnancy BMI, method of conception, PLGF and UtA-RI has a good predictive value for the risk of PE in twin-pregnant women.

Objective:To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province.Methods:One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.Results:Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD. Conclusion:Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients′ medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members′ health management and reproductive decisions.

Delayed lactation activation is a risk factor for early termination of postpartum breastfeeding with high prevalence and adverse effects on the immediate and long-term growth and development of preterm infants,especially very low birth weight infants.This article reviews the delayed lactation activation,evaluation methods of lactation activation in premature mothers and the intervention measures to shorten the delay of lactation activation,in order to provide the basis for the development of relevant studies and the formulation of effective intervention programs.

Objective:To construct a nomogram for predicting unfavorable prognosis at 6 months after moderate and severe traumatic brain injury (msTBI) and validate its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 387 patients with msTBI who were admitted to 904th Hospital of the Joint Logistic Support Force of PLA from January 2020 to December 2022, including 265 males and 122 females, aged 6-97 years [58(47, 68)years]. According to the Glasgow outcome scale (GOS) score at 6 months after injury, the patients were divided into favorable prognosis group (GOS 4-5 points, n=201) and unfavorable prognosis group (GOS 1-3 points, n=186). The clinical characteristics, imaging manifestations, and laboratory test results of the two groups on admission were recorded. Univariate analysis was applied to evaluate the correlation between the aforementioned indicators and the unfavorable prognosis of the msTBI patients at 6 months after injury. Receiver operating characteristic (ROC) curves of single variable and the correlation heatmap among continuous variables were plotted. Lasso regression was used to select variables and multivariate Logistic regression analysis was used to determine independent predictive factors so as to construct Logistic regression equation and plot the nomogram. The internal verification was carried out by means of random and non-random split of data. In random split, the data were divided randomly with a ratio of 6∶4 into training group ( n=232) and verification group ( n=155). In non-random split, the patients admitted from January 2020 to December 2021 were assigned to the training group ( n=260), while those admitted from January 2022 to December 2022 to the verification group ( n=127). Area under the curve (AUC) was used to evaluate the predictive ability of the model in the training group and verification group, calibration curve and Hosmer-Lemeshow (H-L) test to evaluate its goodness of fit, and decision curve analysis (DCA) to evaluate its clinical applicability. The influence of inclusion of neutrophil-to-lymphocyte ratio (NLR) model on the warning effectiveness of poor prognosis was analyzed in comparison with the model without inclusion of NLR. Results:Univariate analysis showed that there was a certain correlation between age, length of hospital stay, Glasgow coma scale (GCS), American Society of Anesthesiologists Physical Status (ASA-PS) classification, Injury severity score (ISS), prehospital tracheal intubation, hypotension, hypoxia, pupillary responsiveness, midline shift, basilar cisterna status, traumatic subarachnoid hemorrhage (tSAH), D-Dimer, prothrombin time activity (PTA), glucose, hemoglobin, K +, Cl -, Ca 2+, HCO -, creatinine, albumin, lactic acid, platelet, lymphocyte, systemic immune-inflammation index (SII), NLR, lymphocyte-to-monocyte ratio (LMR) and unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The ROC curve of single variable showed that GCS (AUC=0.82), ISS (AUC=0.81), pupillary responsiveness (AUC=0.76), basal cistern status (AUC=0.73) and NLR (AUC=0.73) had good predictive validity. The results of the correlation heatmap showed that there was a significant correlation and collinearity among the continuous variables, while no collinearity was found between ISS and NLR. Fourteen potential predictors selected by Lasso regression were included in multivariate Logistic regression analysis and its results showed that age ( OR=0.86, 95% CI 1.38, 5.19), GCS 6-8 points ( OR=3.13, 95% CI 1.06, 9.27), GCS 3-5 points ( OR=12.36, 95% CI 2.81, 54.27), ISS ( OR=3.68, 95% CI 1.38, 9.80), pupillary responsiveness ( OR=2.45, 95% CI 0.85, 7.07), and NLR ( OR=2.62, 95% CI 1.52, 4.51) were identified as the independent risk factors for unfavorable prognosis of msTBI patients at 6 months after injury ( P<0.05 or 0.01). The multivariate Logistic regression equation was Logit [P/(1-P)]=0.066×"age"+ 1.474×"GCS 6-8"+2.357×"GCS 3-5"+0.066×"ISS"+0.965×"absence of pupillary light reflex"+0.194×"NLR"-10.704. In the internal verification of random split of data, the AUC value of the model was 0.93 (95% CI 0.89, 0.96) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. In the internal verification of non-random split, the AUC value was 0.94 (95% CI 0.91, 0.97) in the training group and 0.93 (95% CI 0.89, 0.97) in the verification group. The calibration curve and H-L test showed that the model had good calibration ability ( P>0.5). The results of DCA showed that the application of the nomogram would increase the net benefit of the patients (risk threshold probability of 0.0-0.8). Compared with the conventional model (AUC=0.90), inclusion of NLR model (AUC=0.93) enhanced the warning effectiveness. Conclusions:Age, GCS, ISS, pupillary responsiveness and NLR are independent risk factors affecting unfavorable prognosis in msTBI patients at 6 months after injury, based on which the nomogram constructed can better predict the clinical outcome of msTBI patients.

Delayed lactation activation is a risk factor for early termination of postpartum breastfeeding with high prevalence and adverse effects on the immediate and long-term growth and development of preterm infants,especially very low birth weight infants.This article reviews the delayed lactation activation,evaluation methods of lactation activation in premature mothers and the intervention measures to shorten the delay of lactation activation,in order to provide the basis for the development of relevant studies and the formulation of effective intervention programs.