Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Cerebellar hemorrhage（CBH）in preterm infants is a significant risk factor affecting the neurodevelopmental prognosis of preterm infants，with an increasing incidence over time.Early intervention and treatment by analyzing the risk factors of CBH can improve the survival rate and quality of life for preterm infants.However，there is currently limited research on the risk factors associated with CBH in preterm infants.Cranial ultrasound is the preferred neuroimaging method for diagnosing CBH.With advancements in ultrasound technology，the diagnostic rate of CBH has improved.This article provides a comprehensive review of the risk factors of CBH in preterm infants and the progress on cranial ultrasound diagnosis research，aiming to strengthen the diagnosis，treatment，and follow-up care of cerebellar hemorrhage in preterm infants.

Objective To investigate corneal biomechanical differences in different geometric design parameters of orthokeratology lenses(OK lenses)and to further reveal the corneal shaping mechanism of OK lenses.Methods A coupled finite element model of the aspheric OK lens corneosclera was established for various geometric design parameters of the OK lens,corresponding to different degrees of myopia correction.The distribution trends of the profile and curvature of the corneal anterior surface,as well as the von Mises stress(VMS)and eye axis displacement on both the corneal anterior surface and superior corneal stroma surface were analyzed numerically.Results The stress concentration of the corneal anterior surface was observed in the mid-peripheral and peripheral zones,whereas that of the superior corneal stroma surface appeared in the mid-peripheral zones.The sagittal height of the base curve of the OK lens decreased with increasing degree of myopia correction.At myopia correction degrees of-2.0,-3.0,-4.0,-5.0,and-6.0 D,the maximum corneal VMS increased by 0.81%,1.86%,2.84%,3.81%,and 7.04%,respectively,compared with that at-1.0 D;the curvature of the corneal central zone was reduced by an average of 2.59,3.78,4.51,4.99,5.33,and 6.41 D compared with that without OK lenses.Conclusions The sagittal height of the base curve of the OK lens decreased with increasing degree of myopia correction,resulting in a flatter central curvature of the cornea.The base curve of the OK lens plays a crucial role in both correction and control of myopia.

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.

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*

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 lm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscrip-tomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

Objective: The present study was aimed to explore the role and distinctive mechanism of SPIDR, the key regulatory protein of homologous recombination pathway, in progression of small cell lung cancer (SCLC). Methods: 60 SCLC specimens and 44 normal lung tissues were collected from the patients undergoing tumor resection and bronchoscopic puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2013 to January 2015. The expression of SPIDR in clinical samples and NCIH446 (SCLC cell line) and MRC-5 (normal cell line) were assayed by Real-time PCR. The role of SPIDR in SCLC was investigated in vivo and in vitro by the expression of SPIDR were artificially modified in NCI-H446. Results: Smoking was significantly associated with the occurrence of SCLC (P<0.01). The expression of SPIDR mRNAin SCLC tissues was lower than that of normal lung tissues (P <0.01), and the SPIDR transcriptional and translational levels of NCI-H446 cells were also lower than that of MRC-5.Although there is no significant changes of cell growth rate and susceptibility to cisplatin and etoposide in the NCI-H446 cells overexpressing SPIDR. However, the volume of xenograft tumors of overexpressed SPIDR group decreased by 58.99% (P<0.01) and 61.84% (P<0.01) than that of the original NCI-H446 cells and the NCI-H446 cells transfected with vector (pMSCV) and the average tumor mass decreased by 61.70% (P<0.01) and 70.25% (P<0.01) respectively. When the fetal bovine serum content in the medium was reduced to 3%, the growth rate of NCI-H446 cells overexpressing SPIDR was 22.33% (P<0.01) and 20.24% (P<0.05) lower than that of the original NCIH446 cells and control group, the similar results were obtained from the 1% serum concentration experiment as well. Conclusion: The expression of SPIDR, the key regulatory protein in the DNAdouble strand break homologous recombination repair pathway, was significantly suppressed in SCLC tissues, which markedly accelerated the growth of NCI-H446 cells in vivo and reduced the reliance of NCIH446 cells to the serum. The detailed mechanism is worthy of further investigation.

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.