1.Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy.
Hui YU ; Aliya TIEMUER ; Xufeng YAO ; Mingyuan ZUO ; Hai-Yan WANG ; Yi LIU ; Xiaoyuan CHEN
Acta Pharmaceutica Sinica B 2024;14(1):378-391
Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O2⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO‒) generated from the co-existence of NO and O2⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.
2.The value of peripheral blood sIL-2R,CD4+/CD8+and TNF-α in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis
Hui LIU ; Jiangyan GAO ; Lin HUO ; Xiaoguang ZHANG ; Huixiao ZHANG ; Huan ZHANG ; Hongyi FU ; Xianlei WANG ; Hejuan AN ; Yong WANG ; Rui LIU ; Suli CHEN ; Weihong LI
International Journal of Laboratory Medicine 2024;45(6):738-743,750
Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P<0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P<0.05),sIL-2R was positively correlated with TNF-α(P<0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P<0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P<0.05),and CD4+/CD8+was positively correlated with the efficacy(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P<0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P<0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.
3.Effect and mechanism of radiation combined with different decompression loads on acute injury of rat
Min LIU ; Guang-Sheng LIU ; Yang-Kai WANG ; Rui-Yong CHEN ; Ying HE ; Wen-Hui WU
Medical Journal of Chinese People's Liberation Army 2024;49(3):323-328
Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P>0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P<0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P>0.05),and increased at 72 h(P<0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P<0.05),and a decrease in SOD activity(P<0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P<0.05),and decrease in activity of SOD(P<0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P<0.05),and SOD activity was increased at 72 h in all groups(P<0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.
4.PRMT7 Regulates Adipogenic Differentiation of hBMSCs by Modulating IGF-1 Signaling
Qian GUO ; Jia QING ; Da-Zhuang LU ; Xu WANG ; Yang LI ; Hui ZHANG ; Ying-Fei ZHANG ; Yun-Song LIU ; Yong-Sheng ZHOU ; Ping ZHANG
Progress in Biochemistry and Biophysics 2024;51(6):1406-1417
ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.
5.Mid-and long-term efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type of juvenile developmental dysplasia of the hip
Chuan LI ; Dianzhong LUO ; Tang LIU ; Hui CHENG ; Chao SHEN ; Tao YE ; Baochuang QI ; Xuhan MENG ; Zhifang TANG ; Qing Yong XU ; Luqiao PU
Chinese Journal of Orthopaedics 2024;44(6):388-394
Objective:To investigate the mid-and long-term clinical efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type developmental dysplasia of hip (DDH) in adolescents.Methods:A total of 28 adolescent DDH patients with unilateral dislocation who underwent modified Colonna capsular arthroplasty from January 2016 to January 2018 in the 920th Hospital of Joint Logistics Support Force of People's Liberation Army were retrospectively analyzed. There were 4 males and 24 females, aged 16.5±5.0 years (range, 10-25 years). The mean body mass index was 21.2±1.1 kg/m 2 (range, 18.7-24.1 kg/m 2). According to DDH classification, 10 cases were Tonnis type III and 18 cases were Tonnis type IV. The postoperative lateral center-edge angle, acetabular coverage, femoral anteversion angle and leg length discrepancy were measured. The operation time, intraoperative blood loss, visual analogue scale (VAS) of hip pain, Harris hip score (HHS) and congenital dislocation of the hip score were recorded. Results:All patients successfully completed the operation and were followed up for 72.1±5.2 months (range, 60-84 months). The operation time was 81.6±4.3 min (range, 70-90 min), the intraoperative blood loss was 177.5±12.6 ml (range, 160-200 ml), and the hospital stay was 6.8±0.7 days (range, 6-9 days). The VAS score of the hip joint was 1.8±0.6 before operation and 2.3±0.6 at the last follow-up, and the difference was not statistically significant ( t=2.845, P=0.224). The preoperative HHS score was 57.1±5.9, and it increased to 87.3±4.0 at the last follow-up, and the difference was statistically significant ( t=-22.141, P=0.001). At the last follow-up, the femoral anteversion angle was 17.0°±1.5°, which was lower than that before operation 41.6°±2.4°, with a statistically significant difference ( t=-44.868, P=0.008). The leg length discrepancy was 10.2±2.3 mm, which was lower than that before operation (26.4±6.1 mm), with a statistically significant difference ( t=-12.892, P<0.001). The lateral center-edge angle was 28° (26°, 30°), and the acetabular coverage rate was 78% (76%, 79%). The curative effect evaluation standard score of congenital dislocation of the hip was 24 (16.7, 25.7) points, including 7 excellent cases, 14 good cases, 4 fair cases, and 3 poor cases. The excellent and good rate was 75% (21/28). Conclusion:The modified Colonna arthroplasty for the treatment of unilateral dislocation DDH in adolescents has good mid-and long-term hip function recovery and radiographic improvement.
6.Chronic Fatigue Syndrome Treated with Massage Combined with Aromatic Therapy in 34 Cases: A Randomized Controlled Study
Shuangyun WU ; Yong FU ; Hui LIU ; Tian ZHANG ; Linhui LI ; Haifeng ZHANG
Journal of Traditional Chinese Medicine 2024;65(12):1249-1254
Obejective To investigate and compare the clinical efficacy of aroma massage with traditional massage in the treatment of chronic fatigue syndrome (CFS). MethodsSeventy-two CFS patients were randomized into the aroma massage group and the traditional massage group, with 36 patients in each group. Both groups were treated with essential oil aromatherapy and massage were performed on the head, face, and abdomen stimultaneously. The aroma massage group used antifatigue oil, while the traditional massage group used placebo essential oil. The two groups were treated for 30 minutes each time, once every other day, three times a week, for a total of 4 weeks. The fatigue scale (FS-14) score, traditional Chinese medicine (TCM) syndrome score and patient satisfaction evaluation scale score before and after the treatment of the two groups were assessed to study the improvement of fatigue and other clinical symptoms of the patients as well as the changes of the TCM symptom scores, and to evaluate the clinical efficacy of the two groups. ResultsWith three drop-outs in the traditional massage group and two drop-outs in the aroma massage group, 33 cases in the traditional massage group and 34 cases in the aroma massage group were included in the outcome analysis. The FS-14 scores and TCM syndrome scores significantly decreased after treatment in both groups (P<0.01); compared to those in the traditional massage group (FS-14: 4.42±2.44; TCM syndrome score: 34.12±7.67), the FS-14 score (3.06±2.37) and TCM syndrome score (28.79±5.62) in the aroma massage group were significantly lower (P<0.05 or P<0.01). There was no significant difference in the satisfaction scores of the patients in the two groups after the treatment (P>0.05). The total effective rate of the aroma massage group was 94.12% (32/34), which was significantly higher than 84.85% (28/33) of the traditional massage group (P<0.05). ConclusionBoth aromatherapy and traditional massage can improve the clinical symptoms of fatigue in CFS patients, and aromatherapy is more effective, which is easy to operate with high patient acceptance.
7.Early outcomes of self-expanding interventional pulmonary valve in transthoracic implantation: A prospective clinical study
Ying HUANG ; Ziqin ZHOU ; Yong ZHANG ; Xiaohua LI ; Nianjin XIE ; Hongwen FEI ; Hui LIU ; Junfei ZHAO ; Jian ZHUANG ; Jimei CHEN ; Shusheng WEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):872-877
Objective To evaluate early outcomes of transthoracic pulmonary valve implantation for the treatment of moderate and severe pulmonary regurgitation by using homemade self-expanding valve (SalusTM). Methods Patients with severe pulmonary regurgitation who underwent transthoracic pulmonary valve implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to November 25, 2022 were prospectively enrolled. The early postoperative complications and improvement of valve and heart function were summarized and analyzed. Results A total of 25 patients were enrolled, including 16 males and 9 females, with an average age of 24.5±1.5 years and an average weight of 57.0±3.0 kg. The mean systolic diameters of the bifurcation near the main pulmonary artery, the stenosis of the middle segment of the aorta and near the valve of the right ventricular outflow tract of the patients were 31.8±7.4 mm, 30.6±5.9 mm and 38.4±8.0 mm, respectively. All patients were successfully implanted with valves, and there were no serious complications such as death, coronary compression, stent fracture, valve displacement and infective endocarditis in the early postoperative period. The indexed left atrial longitudinal diameter, indexed right atrial longitudinal diameter, and indexed right ventricular outflow tract anteroposterior diameter decreased significantly after the operation. The degree of tricuspid and pulmonary valve regurgitation and the indexed regurgitation area decreased significantly. The above differences were statistically significant (P<0.05). Conclusion The early outcomes of transthoracic pulmonary valve implantation with homemade self-expanding pulmonary valve (SalusTM) in the treatment of severe pulmonary regurgitation is relatively good, and the long-term outcomes need to be verified by the long-term follow-up studies with large samples.
8.Domestic self-expanding interventional pulmonary valve stent in transthoracic implantation for pulmonary valve regurgitation: A prospective cohort study
Ziqin ZHOU ; Taoran HUANG ; Naijimuding ABUDUREXITI ; Yong ZHANG ; Haiyun YUAN ; Nianjin XIE ; Hongwen FEI ; Hui LIU ; Jian ZHUANG ; Jimei CHEN ; Shusheng WEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1305-1312
Objective To analyze and summarize the early and medium-term outcomes of self-expanding interventional pulmonary valve stent (SalusTM) for right ventricular outflow tract dysfunction with severe pulmonary valve regurgitation. Methods We established strict enrollment and follow-up criteria. Patients who received interventional pulmonary valve in transthoracic implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to July 18, 2023 were prospectively included, and all clinical data of patients were collected and analyzed. Results A total of 38 patients with severe pulmonary regurgitation were included, with 23 (60.5%) males and 15 (39.5%) females. The mean age was 24.08±8.12 years, and the mean weight was 57.66±13.54 kg. The preoperative mean right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) were 151.83±42.84 mL/m2 and 83.34±33.05 mL/m2, respectively. All patients successfully underwent transcatheter self-expandable pulmonary valve implantation, with 3 (7.9%) patients experiencing valve stent displacement during the procedure. Perioperative complications included 1 (2.6%) patient of postoperative inferior wall myocardial infarction and 1 (2.6%) patient of poor wound healing. The median follow-up time was 12.00 (6.00, 17.50) months. During the follow-up period, there were no deaths or reinterventions, and no patients had recurrent severe pulmonary regurgitation. Three (7.9%) patients experienced chest tightness and chest pain, and 1 (2.6%) patient developed frequent ventricular premature beats. Compared with preoperative values, the right atrial diameter, right ventricular diameter, and tricuspid annular plane systolic excursion were significantly reduced at 6 months and 1 year postoperatively, with improvement in the degree of pulmonary regurgitation (P<0.01). Compared with preoperative values, RVEDVI and RVESVI decreased to 109.51±17.13 mL/m2 and 55.88±15.66 mL/m2, respectively, at 1 year postoperatively (P<0.01). Conclusion Self-expanding interventional pulmonary valve in transthoracic implantation is safe and effective for severe pulmonary valve regurgitation and shows good clinical and hemodynamic results in one-year outcome.
9.Establishment and evaluation methods of a novel animal model of liver depression transforming into fire syndrome-related depression
Dan SU ; Jian LI ; Gen-hua ZHU ; Ming YANG ; Liang-liang LIAO ; Zhi-fu AI ; Hui-zhen LI ; Ya-li LIU ; Yong-gui SONG
Acta Pharmaceutica Sinica 2024;59(6):1680-1690
Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and
10.Establishment and evaluation of a rapid PCR-colloidal gold test strip method for the detection of Fritillaria ussuriensis
Yu-he MA ; Cong-hui SHANG ; Qiu-he MA ; Tao LI ; Yue LIU ; Bei-zhen PAN ; Li-jun GAO ; Ming-cheng LI ; Wei XIA ; Yong-mei QU
Acta Pharmaceutica Sinica 2024;59(6):1773-1778
This study design of specific identification primers for the ITS2 sequence of

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