A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors / 医学前沿

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

Clinical significance of CD34 / 医学前沿

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34

Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia / 医学前沿

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as DUX4 rearrangements, MEF2D rearrangements, ZNF384/ZNF362 rearrangements, NUTM1 rearrangements, BCL2/MYC and/or BCL6 rearrangements, ETV6-RUNX1-like gene expression, PAX5alt (diverse PAX5 alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic PAX5 alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study

Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65x109/L vs. 0.76x109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials. Significance StatementCOVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explored the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was welltolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 days. Radiological examination showed varying degrees of absorption of lung lesions within 7 days. These results indicate that CP can serve as a promising rescue option for severe COVID-19 while the randomized trial is warranted.

Phase adjusted estimation of the number of 2019 novel coronavirus cases in Wuhan, China

An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV / SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6 or 3.1. The number of infections would reach 11,044, 70,258 and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6 and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public heath intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077-84,520 or 55,869-81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.

Discussion on Experience of ZHANG Liang-ying in Treating Polycystic Ovary Syndrome ;Combined with Dysfunctional Uterine Bleeding / 中国中医药信息杂志

Polycystic ovary syndrome (PCOS) and dysfunctional uterine bleeding (DUB) are common gynecologic endocrine diseases, and their etiology, pathology, diagnosis and treatment are related but also distinguishing. Some patients have PCOS and DUB at the same time, which is difficult to cure. Professor ZHANG Liang-ying has treated these patients with staging treatment based on syndrome differenciation, and has received desiable efficacy.

Introduction of Experience of Professor ZHANG Liang-ying's TCM Adjunctive Therapy for IVF-ET / 中国中医药信息杂志

Professor ZHANG Liang-ying in Yunnan University of Traditional Chinese Medicine conducted TCM adjuvant therapy for in vitro fertilization - embryo transfer (IVF-ET) of infertility patients, which has obtained satisfactory results. The use of kidney-based, disease differentiation combined with the treatment, emphasizing preoperative conditioning, psychological adjustment, and appropriate choice, can help improve the IVF-ET pregnancy rate and complications of many problems.

Bioinformatics of tumor molecular targets from big data / 中华胃肠外科杂志

The big data from high throughput research disclosed 4V features: volume of data, variety of data, value for deep mining, and velocity of processing speed. Regarding the whole genome sequencing for human sample, at average 30x of coverage, a total of 100 GB of original data (compression FASTQ format) could be produced. Replying to the binary BAM format, a total of 150 GB data could be produced. In the analysis of high throughput data, we need to combine both clinical information and pathological features. In addition, the data sources of medical research involved in ethical and privacy of patients. At present, the costs are gradually cheaper. For example, a whole genome sequencing by Illumina X Ten with 30x coverage costs about 10,000 RMB, and RNA-seq costs 5000 RMB for a single sample. Therefore, cancer genome research provides opportunities for discovery of molecular targets, but also brings enormous challenges on the data integration and utilization. This article introduces methodologies for high throughput data analysis and processing, and explains possible application on molecular target discovery.

Organ allografts combined with hematopoietic stem cell transplantation and immunotolerance / 中华肝胆外科杂志

Our understanding of the immunological mechanisms of rejection has greatly improved over the past 10 years. The allografts have maintained long survival without immunosuppressive treatment in the several organ-transplant recipients combined with hematopoietic stem cell transplantation. The authors attributed the successful outcome to the cotransplantation of donor stem cells. The review will analyze firstly conditions of the recipients, and then review the theoretical basis and history regarding donor-specific tolerance of allograft, and it will also clarify that there is no direct link between the donor-specific transplantation tolerance and hematopoietic stem cell transplantation.

Effect of Therapy of Tonifying Kidney and Replenishing Essence on Protein Expression Profile in Testes of Aged Rats / 广州中医药大学学报

Objective To observe the effects of therapy of tonifying kidney and replenishing essence on protein expression profile in testes of aged rats.Methods Twenty male SD rats with 22 months old were equally randomized into the blank control group and the treatment group.The treatment group received gastric gavage of herbs at the dose of 0.05g?kg-1.d-1,which has the actions of tonifying kidney and replenishing essence.The treatment lasted 60 days.After treatment,the right testes were taken out from the rats,and the differentially expressed proteins in the rats testes of two groups were analyzed by two-dimensional gel electrophoresis(2-DE).Results Compared with the model group,obvious changes were found in 7 kinds of differentially expressed proteins in rats testes of the treatment group,of which 4 kinds were up-regulated and 3 down-regulated.After digestion and identification by the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum,5 kinds from the 7 kinds of proteins were identified as phosphatidyl ethanolamine-binding protein(PEBP),heat shock 70 kDa protein 8,triose-phosphate isomerase,glyceraldehyde-3-phosphate dehydrogenase(GAPDH),and glutathione S-transferase Mu 1(GSTM1-1).Conclusion The anti-aging mechanism of therapy of tonifying kidney and replenishing essence is probably related with the regulation of testis protein expression in aged rats.

Research on improving the surgery skills of the interns of clinical medicine / 中华医学教育探索杂志

Objective To research the value of using constant circling individual training program to improve surgery clinical skills of clinical medical specialty interns.Method 42 interns were divided into 3 groups:A(excellent),B(medium) and C(poor) according to their scores in entrance clinical skill test and each group would perform respective training program including conventional training,unified intensive training and intensive training in person.Their performance would be scored six times during the whole process of training.Results Compared with the final scores with beginning scores,the number of students scored A increased significantly meanwhile the number of students scored C decreased obviously.Conclusion The constant circling individual training program combined with effective unified test can benefit improving the surgery clinical skills of the interns of clinical medicine.