Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct^+/+ mice, placentae and embryos (Qpct^-/+ and Qpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct^+/+ and Qpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct^+/+ and 3285 Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct^-/+ and Qpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals ; Female ; Pregnancy ; Mice ; Placentation/genetics* ; Single-Cell Analysis ; Gene Expression Profiling ; Mice, Knockout ; Transcriptome ; Placenta/blood supply* ; Neovascularization, Pathologic/genetics* ; Genomic Imprinting ; Single-Cell Gene Expression Analysis ; Angiogenesis

OBJECTIVE: To analyze the medical equipment operation data of 44 clinical departments in the hospital from three aspects: materials and consumables, operation and maintenance depreciation, and operation management. METHODS: To formulate the evaluation standards and scoring criteria for the operation indicators, the lowest score is 0 points, and the highest score is 5 points. Based on the operation indicators of medical equipment, establish a hierarchical structure model, determine the criterion layer and sub-criteria layer, construct a judgment matrix, normalize it, and calculate the weight coefficient. RESULTS: Count equipment operation data in 2021 and 2022. Score according to the assessment standards, assign weights through the analytic hierarchy process, calculate the total score and sort, and making a special analysis on the top 10 departments and departments with a score below 4 points, and formulate a rectification plan. CONCLUSIONS The establishment of index assessment standards and the weight distribution of AHP can effectively enhance the control of equipment operating costs.
Analytic Hierarchy Process ; Rationalization ; Surgical Equipment ; Reference Standards ; Cost Control

The parabrachial nucleus (PBN) integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing, emotion, and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem. However, the precise identity and function of distinct PBN subpopulations are still largely unknown. Here, we leveraged molecular characterization, retrograde tracing, optogenetics, chemogenetics, and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain, rather than the medulla. Their activation induces freezing and anxiety-like behaviors, which in turn result in tachypnea. In addition, optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture. We propose that these neurons comprise a PBN subpopulation with specific gene expression, connectivity, and function, which play essential roles in behavioral and physiological regulation.
Parabrachial Nucleus/physiology* ; Wakefulness/physiology* ; Neurons/physiology* ; Emotions ; Sleep

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

ObjectiveTo explore the clinical efficacy and safety of the combination of Erchentang and Bixie Fenqingyin in the treatment of patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome to provide a new method and evidence for the treatment of acute cerebral infarction with hyperuricemia. MethodA total of 132 eligible patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome admitted to the Putuo Hospital of Shanghai University of Traditional Chinese Medicine（TCM） from May 2021 to May 2022 were randomly divided into a Chinese medicine group， a western medicine group， and a control group， with 44 cases in each group. All three groups received routine western medical treatment for acute cerebral infarction. Additionally， the Chinese medicine group received Erchentang combined with Bixie Fenqingyin， the western medicine group received Benzbromarone tablets， and the control group did not receive any uric acid-lowering treatment. The treatment duration was four weeks. The modified Rankin Scale （mRS） score after three months of onset， as well as the National Institutes of Health Stroke Scale （NIHSS） scores， TCM syndrome scores， serum uric acid （SUA） levels， serum C-reactive protein （CRP） and interleukin-6 （IL-6） levels， serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels， and other safety indicators were observed before and after treatment. ResultA total of 129 cases completed the trial observation， with 43 cases in the Chinese medicine group， 42 cases in the western medicine group， and 44 cases in the control group. The rate of good prognosis in the Chinese medicine group （83.7%，36/43） was higher than that in the western medicine group （64.3%，27/42） and the control group （40.9%，18/44） （χ²=4.184，16.930，P<0.05）， and the western medicine group was superior to the control group （χ²=4.707，P<0.05）. After treatment， the NIHSS scores， TCM syndrome scores， SUA， CRP， IL-6， and MDA levels of the patients in all three groups decreased， while the SOD levels increased compared with those before treatment （P<0.05）. Among them， the improvement in NIHSS score was better in the Chinese medicine group and the western medicine group than in the control group （P<0.05）. The Chinese medicine group showed the greatest improvement in TCM syndrome （P<0.05）， while the western medicine group showed the greatest reduction in uric acid levels （P<0.05）. No significant abnormalities in safety indicators were observed before and after treatment in the three groups， and no serious adverse reactions were reported. ConclusionThe combination of Erchentang and Bixie Fenqingyin can significantly improve the prognosis， early neurological deficits， and TCM syndromes of patients acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome. It can also lower uric acid levels and inhibit inflammatory and oxidative stress reactions.

Low-intensity transcranial ultrasound stimulation(LITUS),a high-resolution and safe neuromodulation technique,holds great promise as a treatment option for alleviating both motor and non-motor symptoms in Parkinson disease. This article presents a comprehensive overview of the application of LITUS in the rehabilitation of Parkinson disease from the aspects of the parameters,classification,efficacy,and mechanism of LITUS.

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.