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 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.

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.

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 assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases. METHODS: A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). RESULTS: Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%). CONCLUSION Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.
Child ; Infant, Newborn ; Humans ; Female ; Prospective Studies ; Connexins/genetics* ; Connexin 26/genetics* ; Glucosephosphate Dehydrogenase Deficiency ; Mutation ; Sulfate Transporters/genetics* ; DNA Mutational Analysis ; Genetic Testing/methods* ; Deafness/genetics* ; Neonatal Screening/methods* ; Hearing Loss, Sensorineural/genetics* ; High-Throughput Nucleotide Sequencing ; Solute Carrier Family 22 Member 5/genetics*

Objective To explore the effect of Linc00460 on the aerobic glycolysis of breast cancer (BC) cells through sponge adsorption of miR-320a. Methods The qRT-PCR method was used to detect Linc00460 and miR-320a expression levels in normal breast epithelial cell line MCF-10A and five BC cell lines. The effect of interfering Linc00460 on miR-320a expression was detected by qRT-PCR. The double luciferase reporter gene experiment was used to analyze the targeting relationship between miR-320a and Linc00460. In addition, the si-Linc00460 and miR-320a inhibitor were co-transfected into MDA-MB-231 cells, and the expression level of miR-320a in the cells was detected by qRT-PCR; cell proliferation ability was measured by the MTT method; glucose uptake rate was detected by 2-NBDG method; the content of lactic acid in the cell supernatant was detected by colorimetric method; the key enzymes of glycolysis was detected by the enzyme activity kit; and the expression levels of the key proteins in the glycolysis pathway were detected by Western blot. Results Linc00460 was highly expressed in five BC cell lines, while miR-320a was lowly expressed as compared with MCF-10A cells. The expression of miR-320a in MDA-MB-231 cells significantly increased after interfering with Linc00460. The double luciferase reporter gene experiment confirmed that miR-320a and Linc00460 could target binding. Interfering with the expression of Linc00460 could inhibit MDA-MB-231 cells proliferation (all P=0.000), reduce the rate of cellular glucose uptake and the content of lactic acid in the cell supernatant (all P=0.000), inhibit the activities of PFK, PK, and LDH enzymes (all P=0.000), and downregulate the protein expression levels of PFKM, GLUT1, and LDHA (all P=0.000). Meanwhile, inhibition of miR-320a could reverse the inhibitory effect of si-Linc00460 on the proliferation and glycolysis of MDA-MB-231 cells (all P=0.000 or 0.001). Conclusion Linc00460 might adsorb miR-320a, consequently leading to upregulation of PFKM expression, thereby promoting aerobic glycolysis in BC cells.

Frailty is the clinical syndrome that occurs due to an increase in personal vulnerability and a decline in the ability to maintain one′s internal balance, which is closely related to the development of bladder cancer in the elderly. The research on frailty of elderly patients with bladder cancer in China is still in its infancy. This article discussed the risks of bladder cancer and frailty, the necessity of preoperative frailty assessment in patients with bladder cancer, commonly used assessment tools, and summarized the limitations of the existing evaluation tools to provide reference for further developing and improving the frailty evaluation tools and applications for bladder cancer patients research provides reference.

OBJECTIVE：To rapidly evaluate the effectiveness ，safety and economy of evolocumab in the treatment of hypercholesterolemia so as to provide evidence-based reference for clinical drug selection and decision. METHODS ：Retrieved from PubMed，Cochrane Library ，CNKI，Wanfang database and HTA relative official website ，HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic studies about evolocumab alone or combined with standard plan versus standard plan or placebo or ezetimibe in the treatment of hypercholesterolemia were collected during the inception to Jan. 2020. Based on literature screening and data extraction ，HTA checklist ，system evaluation measurement tool AMSTAR- 2 scale，comprehensive healthy economic evaluation report standard scale were used to evaluate the quality of included HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic literatures. Quantitative description was performed for effectiveness and safety results ，and qualitative description was performed for economic evaluation results. RESULTS ：A total of 13 literatures were included ，involving 6 Meta-analysis and 7 economic studies. The quality of Meta-analysis literatures was low ，and the quality of economic research was good. In terms of effectiveness ，compared with placebo or ezetimibe ，evolocumab significantly reduced the levels of LDL-C ，TC， TG and VLDL-C ，the incidence of cardiovascular events ，myocardial infarction ，coronary ischemia and stroke ，while increased the level of HDL-C （P＜0.05）. There was no statisti cal significance in the risk of hospitalizatio n，cardiac mortality or cardiovascular disease mortality in patients with unstable angina pectoris between placebo and evolocumab （P＞0.05）. In terms ofsafety，there was no significant difference in the incidence of 6237545。E-mail：zhangxu1130@163.com any adverse events ，any treatment emergency adverse events and back pain ，musculoskeletal and connective tissue diseases between evolocumab and placebo （P＞0.05）. In terms of economy，additional use of evolocumab ，based on standard plan ，had a cost-effectiveness advantage for patients with high-risk atherosclerotic cardiovascular disease （ASCVD）whose blood lipids were still not up to standard. CONCLUSIONS ：Evolocumab has good effectiveness and safety in the treatment of hypercholesterolemia. For high-risk patients with ASCVD whose blood lipids are still not up to standard after standard plan ，evolocumab has certain economy and can be used as an alternative.