Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium unveiled numerous research advances which provide meaningful insights into the selection of treatment regimens of prostate cancer. Precision multi-treatment based on patients’ characteristics has become the predominant approach, including the use of a three-drug combination therapy for metastatic hormone-sensitive prostate cancer, and poly adenosine diphosphate ribose polymerase inhibitor therapy for metastatic castration-resistant prostate cancer. Nuclear medicine therapy and radiotherapy are also receiving significant attention. Integrated nuclear medicine diagnosis and therapy show immense potential for non-metastatic castration-resistant prostate cancer. Additionally, for localized prostate cancer, stereotactic body radiotherapy is a preferred alternative to surgery. This article sheds light on several key studies presented at the conference, focuses on prostate cancer treatment at different stages, and intends to enhance the therapeutic outcome for prostate cancer patients.

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective To explore the clinical features, treatment and follow-up of Cockayne syndrome with renal involvement. Method The clinical data of one child with Cockayne syndrome confirmed by gene detection with renal injury were reviewed, and the clinical features of renal involvement in Cockayne syndrome were summarized. Results A male child aged 3 years and 8 months had clinical manifestations of mental retardation, growth retardation, special face and photosensitive dermatitis, and renal involvement was manifested by nephrotic syndrome. Cranial CT showed symmetrically calcification in bilateral basal ganglia. The targeted next generation sequencing results showed homozygous mutations of c.394_398del and p.Leu132Asnfs in ERCC8 gene (NM_000082) of the child, and the same heterozygous mutation was found in both his parents (non-consanguineous marriage). After the diagnosis of nephrotic syndrome, full dose prednisone was given for experimental treatment. The urine protein decreased but did not disappear, which was considered hormone resistance. After 4 months of combined treatment with cyclosporin, the urine protein turned negative. During 20 months of follow-up, urine protein remained negative and renal function remained stable. The renal involvement in Cockayne syndrome was seldomly reported, and its clinical manifestations are heterogeneous. Condusion Renal involvement in Cockayne syndrome may be manifested with nephrotic syndrome which should be noticed.

Objective To study the neurological prognosis of neonates with ventriculomegaly and its influencing factors.Method A retrospective study was conducted among neonates with ventriculomegaly in Peking University First Hospital from January 2013 to December 2015.A series of cranial ultrasonography were performed after birth and the Gesell development scale was conpleted after six months.x2 test and two-independent-sample t test were used for statistical analysis.Result Among 103 cases of ventriculomegaly,95 cases (92.2％) had mildly enlarged lateral ventricles and 8 cases (7.8％) significantly enlarged.83 cases received serial cranial ultrasound examinations after birth.The lateral ventricles of 9 patients (10.8％) bacame wider and 74 (89.2％) not.The Gesell development scales were completed in 65 cases 6 months after birth.Among them,8 patients with widening lateral ventricles got poor prognosis (100％).Among 57 patients without progressively widening lateral ventricles,6 (10.5％) had poor prognosis.The difference was statistically significant (P ＜ 0.001).No correlation was found between the severity of the lateral ventricle widening and the neurological outcome (P =1.000).There were 2 cases with other abnormalities,and 1 case got poor prognosis on follow-up.Conclusion Most neonatal ventriculomegaly patients have mild and isolated lateral ventricle enlargement.Most of them remain stable or gradually return to normal.The patients with progressively widening lateral ventricles are likely to have adverse neurological prognosis.

Objective To study the characteristics and its risk fastors of brain development of the preterm infant early after birth in amplitude-integrated electroencephalography(aEEG). Methods The 153 preterm infants who had seen a doctor in Peking University First Hospital from April 2009 to August 2013 accepted the aEEG check at term of corrected gestational age ( ≥ 38 weeks but < 42 weeks of corrected gestational age). The risk factors of brain development, such as gestational age ( < 30, 30 ≤ - ≤ 33+6 and 34≤-≤36+6 weeks), clinical informations [relatively stable group including 104 cases without any serious complications or brain injury, the group only suffering from a serious brain injury (19 cases), and the group only suffering from severe systemic disease (30 cases)] and nutrition (good or malnutrition), were analyzed. Also the relationship between the aEEG and the cranial ultrasound detected at the same time and the Gesell Developmental Scale at six months of corrected gestational age. Theχ2 test, two independent samples t-test and Logistic regression analysis were used for statistical analysis. Results The aEEG of 52%(79/153) cases reached the level of normal full-term newborn at term of corrected gestational age, only 48% (74/153) were abnormal. The abnormal rate of aEEG results in relatively stable preterm infants decreased from 3/6 (<30 weeks) to 35%(13/37) at 34 ≤ - ≤ 36+6 weeks, but the difference was not statistically significant (χ2=1.998, P=0.353). The abnormal rate of aEEG results in the group suffering from a serious brain injury was higher than the relatively stable preterm infants [14/19 vs 44%(46/104) ,χ2=5.578, P=0.024]. In relatively stable preterm infants, there was no difference of the abnormal rate of the aEEG results between intrauterine malnutrition group and good nutrition group [46%(19/41) vs 43%(27/63),χ2=0.122, P=0.727]. Neither was between extrauterine malnutrition group and good nutrition group [52%(13/25) vs 42%(33/79),χ2=0.805, P=0.369]. Serious brain injury was independent risk factor of abnormal aEEG (OR=3.453, 95%CI: 1.177-10.132, P=0.024). The coincidence rate of aEEG and the cranial ultrasound examination or the scores of Gesell Developmental Scale was 57%(56/98) and 50%(10/20), respectively. Conclusions The brain catch-up development may appears early after birth in preterm infants, which are impaired by lower gestational age and the severe brain injury. It is more effective of aEEG for evaluating the brain development of preterm infants when combines with other methods.

Two kinds of different functional groups modified RuBpy-doped silica fluorescent nanoprobes Probe A and B that conjugated with avidin were prepared for the recognition of liver cancer cells. Firstly RuBpy-doped silica nanoparticles were synthesized by reverse microemulsion and modified with different functional groups, then Probe A was prepared by the conjugation of avidin with carboxyl modified nanoparticles through covalent binding using 1-ethyl-3-( 3-dimethylamino propyl ) carbodiimide hydrochloride ( EDC )/sulfo-NHS, whereas Probe B was prepared by the conjugation of avidin with the polyethylene glycol ( PEG) linkers on the surface nanoparticles using cyanogen bromide method. Therefore, compared with Probe A, Probe B was obtained by coupling avidin to the nanoparticles through long-chain PEG molecules. The two probes were incubated with liver cancer cells respectively, and microscopic fluorescence imaging shows that Probe B which contained PEG molecules could be more effectively applied for the recognition of tumor marker carcinoembryonic antigen ( CEA) in liver cancer cells.

Objective To determine the prognosis and risk factors of neonatal cerebral infarction.Methods From January 2002 to December 2010,44 newborn infants were diagnosed with cerebral infarction by imaging examinations at Peking University First Hospital.The neurodevelopmental outcomes of these newborn infants were followed up and evaluated by clinical manifestations,Gesell development scale,cranial imaging,electroencephalogram and auditory evoked potential.Factors related to prognosis were analyzed with single and multi-factor Logistic regression analysis.Results Thirty-eight (86％) cases were followed up,and of these cases,five children died and the results of three were inconclusive due to small age (less than 6 months old).Among the remaining 30 children,neurodevelopmental outcome was normal in 15 cases and abnormal in the remaining 15 cases,thus,the incidence of sequelae was 50％ (15/30) and the mortality rate was 13％ (5/38).Of the 15 abnormal cases,all had cerebral palsy and movement retardation,eight cases had cognitive impairment,eight cases had epilepsy and five had visual impairment.The incidence of large cerebral infarction (more than one lobe) was 14/15,worse cranial imaging outcome (one month after treatment,cerebral infarction lesion still present or had expanded)was 13/15,and severe complications was 8/15 in the newborns with sequelae,which were higher than in those without sequelae (4/15,5/15 and 1/15,respectively) (x2=13.889,8.889 and 7.778,all P＜0.05).Logistic regression analysis showed that large cerebral infarction was a risk factor for sequelae (OR=38.500,95％C1:3.749-395.407,P=0.002),however,worse cranial imaging outcome (OR=8.563,95％CI:0.909-80.683,P=0.061) and severe complications (OR=18.024,95％CI:0.516-630.163,P=0.111) were not risk factors for sequelae.Cerebral infarction with middle cerebral artery injury had a high risk of movement retardation (OR=6.000,95％CI:1.172-3.725,P=0.025),and those with a large cerebral infarction were more likely to have epilepsy (x2=7.273,P=0.010).The incidence of large cerebral infarction in the newborn infants with cognitive impairment was 8/8,which was much higher than in those without cognitive impairment (46％,10/22),thus,infarct area may be related to cognitive ability (x2=7.273,P=0.010).Conclusions Neonatal cerebral infarction might result in many types of sequelae,with motor impairment being the most common form.A large cerebral infarction is more likely to result in abnormal neurodevelopmental outcome.