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381. [Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells].

作者: Yuan Pan.;Hang Gu.;Han Xiao.;Lijun Zhao.;Yiman Tang.;Wenshu Ge.
来源: Beijing Da Xue Xue Bao Yi Xue Ban. 2024年56卷1期9-16页
To explore the effect of ubiquitin-specific protease 42 (USP42) on osteogenic differentiation of human adipose-derived stem cells (hASCs) in vivo and in vitro.

382. [Establishment of acute graft-versus-host disease model after non-myeloablative haploidentical peripheral blood stem cell transplantation in aged mice].

作者: W Y Miao.;J L Xu.;K L Zhang.;H B Wang.;M Jiang.
来源: Zhonghua Yi Xue Za Zhi. 2024年104卷7期540-546页
Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.

383. [The therapeutic effect and prognostic value of oligoclonal bands after autologous stem cell transplant in patients with multiple myeloma].

作者: Q L Shi.;Y Xu.;J Wang.;Y Y Jin.;R Zhang.;J Y Li.;L J Chen.
来源: Zhonghua Yi Xue Za Zhi. 2024年104卷7期514-520页
Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.

384. [The characteristics and impact on prognosis of cytopenia after anti-BCMA-CAR-T therapy in patients with relapsed and refractory multiple myeloma].

作者: X X Shen.;Y Yao.;Y Xia.;Y Y Jin.;R Zhang.;J Y Li.;L J Chen.
来源: Zhonghua Yi Xue Za Zhi. 2024年104卷7期507-513页
Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.

385. [Current status and challenges of immunotherapy for multiple myeloma].

作者: J Lu.;J Y Bi.
来源: Zhonghua Yi Xue Za Zhi. 2024年104卷7期468-472页
Multiple myeloma (MM) is the second most common hematologic malignancy and the incidence of MM in mainland China in 2016 was 1.15/100 000.With the development of China's aging society, the incidence of MM is expected to increase year by year. Immunotherapy for MM has become the fourth pillar of therapy after autologous hematopoietic stem cell transplantation, immunomodulators, and proteasome inhibitors, and is the most active area of MM treatment. Nine new drugs have been approved for multiple myeloma treatment in China, and three are expected to be approved in 2024, which will focus on immunotherapy. There are many ambiguities about the current status of research and utilization in this emerging field in China. Determining the optimal integration of these therapies into the treatment regimen for Chinese MM patients constitutes a critical challenge for clinicians. Immunotherapy for MM primarily encompasses two major categories: antibody-based drug therapy and cellular immunotherapy. Antibody-based medications primarily include monoclonal antibodies, T-cell engagers, IgG-like bispecific antibodies, and trispecific antibodies. Cellular immunotherapy mainly consists of chimeric antigen receptor T (CAR-T) cells, as well as other immune cells such as chimeric antigen receptor natural killer (CAR-NK) cells, dendritic cells, T cell receptor-engineered T cells, and peptide vaccines.This article mainly focuses on the current research status and existing issues of the aforementioned immunotherapy methods, with the aim of providing references for the treatment of MM.

386. [Adipose-derived stem cell-derived exosomes regulate Th2/Treg balance in peripheral blood of AR patients through the mTOR pathway].

作者: Feiyan Han.;Xiaojie Xu.;Ying Wang.
来源: Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024年38卷2期140-145页
Objective:To investigate the mechanism of adipose derived stem cell exosomes(ADSC-exos) regulating Th2/Treg balance in peripheral blood of patients with allergic rhinitis(AR). Methods:Thirty patients with AR who were treated in Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Zhengzhou University from March 2022 to October 2022 were selected, and 30 patients with simple deviation of nasal septum who were treated in our department during the same period were selected as the control group. 10 mL peripheral venous blood was collected from all patients. The levels of IL-4 and TGF-β in plasma were analyzed by ELISA. PBMCs were isolated by density gradient centrifugation. Then, protein and RNA were further extracted, and the expression levels of IL-4, TGF-β, GATA3 and Foxp3 genes were detected by qRT-PCR. Western Blotting detected p-PI3K(P85), p-AKT(Ser473) in PBMCs of AR patients and healthy controls. Protein expression levels of p-mTOR(Ser2448), p-p70S6K(Thr389), and the proportion of Th2 and Treg cells were analyzed by flow cytometry. PBMCs of AR patients were stimulated to differentiate and co-cultured with exosomes of adipose stem cells. p-PI3K(P85), p-AKT(Ser473), p-mTOR(Ser2448) were detected in exosome treated group and untreated group by Western Blotting. The expression level of p-p70S6K(Thr389) protein, the proportion of Th2 and Treg cells were analyzed by flow cytometry, and the levels of IL-4 and TGF-β in the supernatant of cell culture were detected by ELISA. Results:Compared with the control group, the mTOR pathway in peripheral blood of AR group was significantly activated, the level of IL-4 in plasma was increased, and the level of TGF-β was decreased(P<0.05). Compared with the control group, the proportion of Th2 cells in peripheral blood was increased, and the proportion of Treg cells was decreased(P<0.01). Compared with the untreated group, the expression level of mTOR pathway protein decreased, the level of IL-4 decreased, and the level of TGF-β increased. The proportion of Th2 cells decreased, and the proportion of Treg cells increased(P<0.01). Conclusion:There is an imbalance of Th2 and Treg cells in peripheral blood mononuclear cells of AR patients; the PI3K/AKT/mTOR/p70S6K pathway is activated in peripheral blood mononuclear cells of AR patients Exosomes derived from adipose mesenchymal stem cells may regulate Th2/Treg balance in AR patients through the PI3K/AKT/mTOR/p70S6K pathway.

387. [Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice].

作者: Zijing Wang.;Qi Cao.;Shaowei Hu.;Xintai Fan.;Jun Lv.;Hui Wang.;Wuqing Wang.;Huawei Li.;Yilai Shu.
来源: Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024年38卷1期49-56页
Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions(DPOAE) and auditory brainstem response(ABR) in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane(RWM). Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

388. [Preparation of chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and its effects on wound healing of full-thickness skin defects in rats].

作者: Y Liu.;F Cheng.;Z W Wang.;H X Jin.;B Y Cao.;P F You.;A Hu.;X Y Shi.;J Du.;Z X Yuan.
来源: Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2024年40卷1期50-56页
Objective: To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats. Methods: The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β1 (TGF-β1) were detected by Western blotting (n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results: At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group (t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group (t=7.21, P<0.05). Conclusions: The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

389. [Exosomes from ectoderm mesenchymal stem cells inhibits lipopolysaccharide-induced microglial M1 polarization and promotes survival of H2O2-exposed PC12 cells by suppressing inflammatory response and oxidative stress].

作者: X Sun.;H Shi.;L Zhang.;Z Liu.;K Li.;L Qian.;X Zhu.;K Yang.;Q Fu.;H Ding.
来源: Nan Fang Yi Ke Da Xue Xue Bao. 2024年44卷1期119-128页
To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells (EMSCs-exo) for repairing secondary spinal cord injury.

390. [Fabrication and evaluation of composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface].

作者: Z Q Xu.;Y Q He.;J H Huang.;Z W Qiu.;X X Zeng.
来源: Zhonghua Kou Qiang Yi Xue Za Zhi. 2024年59卷2期165-172页
Objective: To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface. Methods: An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment. Results: After alternative loop immersing, the MN's original microholes (20 μm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point (P<0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN (P<0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 (P<0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN (P<0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 (P>0.05). The Avalue of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) (t=-0.25, P<0.001; t=-0.34, P<0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN (P<0.05). Conclusions: HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

391. [Complementary Therapy: Application of Photobiomodulation in Self-Care and Patient Care].

作者: Hsing-Yu Yang.
来源: Hu Li Za Zhi. 2024年71卷1期4-5页
Photobiomodulation (PBM), also known as low-level laser therapy, is a non-invasive light therapy that applies near-infrared light sources near target tissues. PBM allows photons to penetrate tissues and interact with cells, promoting photophysical and chemical changes that result in desired changes at the molecular, cellular, and tissue levels (Oliveira et al., 2022; Shetty et al., 2023). This complementary therapy has garnered significant research attention both domestically and internationally. The results of recent research indicate non-invasive transcranial light stimulation can enhance high-frequency oscillations such as α and β waves, leading potentially to improved cognitive and neurological functions, memory, attention, and emotional status in healthy adults (Shetty et al., 2023). This mode of therapy is recommended as a non-pharmacological intervention for pain relief (Ross, 2022) and has been found to improve oral pain and quality of life in patients with burning mouth syndrome and in those undergoing hematopoietic stem cell transplantation (Camolesi et al., 2022; Chan et al., 2023). Also, PBM has been promoted as a method of enhancing wound healing (Oliveira et al., 2022) and of reducing the respiratory disturbance index in patients with obstructive sleep apnea (de Camargo et al., 2020). Researchers in Taiwan have also applied PBM to alleviate the pain associated with heel prick blood sampling in newborns and suggested using low-level laser therapy as a pain relief measure for full-term newborns undergoing invasive procedures (Wu et al., 2023). For the column in this issue, we have invited domestic nursing and optoelectronic scholars who have conducted extensive research in the field of PBM to explain the related mechanisms, share research findings, and introduce PBM devices that may be used in clinical, home, and school settings. Considering the impact of shift work on sleep among healthcare professionals, we also hope to provide nurses with different insights and options for self-care and patient care through the research and product introductions provided. Finally, an article on assessing aging and promoting health from a traditional Chinese medicine perspective is included to offer nursing professionals a holistic approach to self-care and preventive concepts based on natural rhythms.

392. [Progress and application of liver organoids in the study of liver cancer].

作者: M Wang.;Z Y Xu.;C Yu.;X Y Zhang.;H Y Cao.;Y Ma.
来源: Zhonghua Gan Zang Bing Za Zhi. 2023年31卷12期1332-1335页
The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

393. [Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms].

作者: Q L Chen.;F Qiao.;W T Lu.;H L Shi.;C X Zhou.
来源: Zhonghua Gan Zang Bing Za Zhi. 2023年31卷11期1209-1216页
Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

394. [Exploration of cystathionine β-synthase and cystathionine γ-lyase gene expression poor prognostic predictive value with the application of bioinformatics data mining in liver cancer].

作者: Z J Liu.;Y N Ma.
来源: Zhonghua Gan Zang Bing Za Zhi. 2023年31卷11期1169-1175页
Objective: To study the relationship between cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) genes-related signaling pathways in liver cancer cells. Methods: We conducted a correlation analysis between the clinical features of CBS and CTH gene expression by mining the GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases of liver cancer. Additionally, liver cancer cell lines were verified by immunoblotting. Results: CBS and CTH expressions were significantly lower in tumors than in non-tumors (P < 0.05). COX regression result showed that CBS was an independent risk factor for the poor prognosis of liver cancer cells (HR=0.65, P = 0.02). A univariate logistic regression analysis was performed on the different tumor stages focusing on the CBS gene, which showed that TNM stage II verses I (P = 0.01, OR=0.50), stage III verses I (P = 0.03, OR=0.56), T stage T2 verses T1 (P < 0.01, OR=0.43), and T3 stage verses T1 (P = 0.02, OR=0.54) were significantly lower in liver cancer. TNM stage III verses I (P = 0.01, OR=0.50), Edmondson stage II verses I (P = 0.03, OR=0.48), stage III verses stage I (P < 0.01, OR=0.30), stage IV verses I (P = 0.03, OR=0.22), and T stage T3 verses T1(P = 0.03, OR=0.22) of the CTH gene expressions were significantly lower in liver cancer. GSEA enrichment analysis result revealed that the signaling pathway most correlated with the expression of CTH and CBS genes in liver cancer cells was cytochrome P450 (CYP450) (FDR Q < 0.01, FWER P < 0.01). Western blot results showed that the expression of the CTH downstream protein CSE was reduced in HCC cell lines such as HLE and Hep3B cells compared with the human immortalized liver cell line HL-7702. Conclusion: CBS and CTH gene expressions are lower in tumor tissue than in normal tissue groups. The CBS gene is an independent risk factor for poor prognosis in stem cell carcinoma. The cytochrome P450 is the signaling pathway most closely related to the CBS and CTH genes.

395. [Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema].

作者: Junzhe Chen.;Chengliang Deng.
来源: Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2024年38卷1期99-106页
To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema.

396. [Study on injectable chitosan hydrogel with tendon-derived stem cells for enhancing rotator cuff tendon-to-bone healing].

作者: Huawei Wen.;Qingsong Zhang.;Ming Tang.;Ya'nan Li.;Hongfei Tan.;Yushun Fang.
来源: Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2024年38卷1期91-98页
To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits.

397. [Impact of lithocholic acid on the osteogenic and adipogenic differentiation balance of bone marrow mesenchymal stem cells].

作者: Cui Wang.;Jiao Li.;Lingyun Lu.;Lu Liu.;Xijie Yu.
来源: Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2024年38卷1期82-90页
To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

398. [Exosomes derived from miR-133a-3p engineered mesenchymal stem cells promote myocardial repair in rats after acute myocardial infarction].

作者: L Sun.;W W Zhu.;J Zhang.;P C Zhao.;Y Q Zhu.;F X Zhang.
来源: Zhonghua Xin Xue Guan Bing Za Zhi. 2024年52卷1期72-78页
Objective: To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats. Methods: UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results: Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion: Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.

399. [Sulforaphane reverses Aβ fiber-mediated M1 type microglia polarization and neuroinflammation-mediated necroptosis of neural stem cells by downregulating the MAPK/NF-κB signaling pathways].

作者: J Zhang.;C Yang.;S Zhang.;T Cao.;R Peng.;W Guo.;Y Yan.;S Xie.;X Peng.;T Lü.;T Huang.
来源: Nan Fang Yi Ke Da Xue Xue Bao. 2023年43卷12期2132-2138页
To explore the effects of sulforaphane (SFN) and Aβ25-35 fibers (fAβ25-35) on M1/M2 polarization of BV-2 cells and neuroinflammation-mediated programmed necrosis of neural stem cells.

400. [Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation].

作者: Z Wei.;S Q Feng.;X Y Yi.;Q Luo.;H J Du.;G Y Mei.;R Liu.;H L Yao.;J Han.
来源: Zhonghua Yu Fang Yi Xue Za Zhi. 2023年57卷12期2095-2101页
Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.
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