BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Objective To investigate the effect of onset-to-needle time(ONT)on early neurological deterioration(END)in patients with acute ischemic stroke(AIS).Methods From June 2020 to June 2023,AIS patients receiving intravenous thrombolysis treatment in the Neurology Department of Seventh People's Hospital of Zhengzhou were continuously enrolled.Patients were divided into the END group(n=96)and non-END group(n=293)based on whether their NIHSS score increased by ≥4 points compared to baseline after 24 h.Baseline and clinical data of the two groups were collected,and relevant influencing factors were analyzed through univariate analysis,multivariate analysis,and subgroup analysis.A logistic regression model predicting the occurrence of END in acute stroke patients was constructed,and the model's predictive ability was evaluated by ROC curves.Results The results of the univariate analysis showed that there were statistically significant differences in age,total cholesterol,low-density lipoprotein cholesterol(LDL-C),lipoprotein-associated phospholipase A2(Lp-PLA2),white blood cell count,activated partial thromboplastin time(APTT),and ONT between the END group and non-END group(all P＜0.05).Additionally,there were statistically significant differences in the distribution of cardiac history,infarct location,and TOAST classification between the two groups(all P＜0.05).The results of the multivariable logistic analysis showed that age(OR=1.095,95％CI:1.029-1.165,P=0.004),LDL-C(OR=2.779,95％CI:1.355-5.694,P=0.005),Lp-PLA2(OR=1.007,95％CI:1.001-1.014,P=0.047),complete anterior circulation infarction(compared to lacunar infarction as control,OR=8.045,95％CI:5.175-12.503,P=0.024),cardioembolic stroke(compared to small vessel occlusion patients as control,OR=12.794,95％CI:8.411-19.462,P=0.002),and ONT(OR=1.014,95％CI:1.001-1.026,P=0.029)were independent risk factors for END in patients with AIS.Subgroup analysis based on the NIHSS score at admission showed that for moderate and severe subgroups,each additional minute of ONT increased the risk of END by 1.4％(95％CI:1.001-1.027,P=0.032)and 2.9％(95％CI:1.008-1.050,P=0.006),respectively.A predictive model was established based on the Logistic analysis results,and a nomogram predicting the risk of END outcome was created.The area under the ROC curve was calculated to be 0.922(95％CI:0.859-0.984,P＜0.001),indicating good predictive performance.Conclusions In clinical practice,patients with high-risk factors such as age,LDL-C,Lp-PLA2,TOAST classification,and infarct location should be given more attention.Timely thrombolytic therapy should be initiated,and patients'families should promptly seek medical assistance.Additionally,optimizing the diagnostic and treatment process,reducing ONT,and minimizing the occurrence of END in patients are crucial.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

Delayed diabetic wound healing has placed an enormous burden on society. The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis. Platelet-rich plasma (PRP) gel, a popular biomaterial in the field of regeneration, has limited applications due to its non-injectable properties and rapid release and degradation of growth factors. Here, we prepared an injectable hydrogel (DPLG) based on PRP and laponite by a simple one-step mixing method. Taking advantages of the non-covalent interactions, DPLG could overcome the limitations of PRP gels, which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine (an angiogenesis promoter). DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in type I diabetic rats and normal rats. Taken together, this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

OBJECTIVE: Invent a simulator which provides a simulation of heart rate and respiratory rate to the intelligent sleep monitoring devices based on precision pressure sensors. METHODS: The simulator was composed of control part and simulated silicone doll. The simulated silicone doll contains heartbeat simulator and breathing simulation airbag. Heartbeat and breathing combination pressure signal can be produced according to frequency set values. Frequencies of pressure signal of the simulator were compared with the monitoring results of intelligent sleep monitoring devices with known accuracy to verify the frequency accuracy of pressure signal of the simulator. Verified the repeatability and stability of the simulator with a stopwatch. RESULTS: The heart rate of the simulator was with in ±2 beats per minute of the monitoring results of intelligent sleep monitoring devices and the respiratory rate of the simulator was with in ±2 times per minute of the monitoring results. The repeatability and stability of the simulator was better than ±5% according to results with a stopwatch. CONCLUSIONS It's practicable to use the simulator which provides a simulation of heart rate and respiratory rate to the accuracy test of the intelligent sleep monitoring devices based on precision pressure sensor.

Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.

With the implementation of the new policy for coronary stent centralized volume purchasing in China, the blood pressure sensor at the tip of the catheter, as one of the essential medical instruments for the diagnosis and treatment of coronary artery disease, will meet the new development opportunity of the industry, a number of medical device companies will actively participate in the development and registration of the catheter tip blood pressure sensor. As an invasive blood pressure sensor, the catheter tip blood pressure sensor should meet the current effective industry standard YY 0781-2010, however, there are many problems when using YY 0781-2010 as a blood pressure sensor because of the difference of product structure and working mode. In this paper, the problems about "Operation Manual", "electrical performance" and "safety requirement" in the course of carrying out YY 0781- 2010 with the blood pressure sensor on the tip of catheter are discussed and analyzed in detail, hope to provide some inspiration for more research and development enterprises of blood pressure sensors on the tip of catheters and inspectors of medical device testing institutions, also hope to be able to contribute to the high-quality development of blood pressure sensor industry at the tip of the Catheter.
Blood Pressure ; Catheters ; China ; Equipment Design

Background::A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA.Methods::Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan-Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF.Results::A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8-62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7-60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ± 15.9 mL/h vs. 169.0 ± 15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study. Conclusions::When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice.Registration::Chinese Clinical Trial Registry ( www.chictr.org.cn, ChiCTR-IPR-17012629)

Objective : The CRISPR / dCas9-SAM system was used to explore genes related to the proliferation of gastric cancer cells AGS，and their role in the occurrence and development of gastric cancer was analyzed． Methods : sgRNA was designed for genes with differential expression between gastric cancer and normal gastric tissue， and a lentiviral library was obtained after packaging was constructed．The AGS cells at different time points after the library was infected with AGS cells were used as the screening pressure，and the AGS cells at three time points on days 0，7 and 14 were collected．High-throughput sequencing analyzed sgRNA enrichment in AGS cells at dif- ferent time points after infection to obtain differential genes related to AGS cell proliferation. Results : Bioinformat- ics showed that compared with the 0 d group，42 and 45 negative screening differential genes and 59 and 40 posi- tive screening differential genes were obtained in the 7 d group and 14 d group，respectively．Among them，the 7 d group and the 14 d group had 11 genes in the negative screening and the positive screening． Conclusion In this study，11 genes inhibiting the proliferation of AGS cells were screened，of which 5 were protein-coding genes and 6 were long non-coding RNA ( lncRNA ) genes． 11 candidate genes that promoted AGS cell proliferation were screened，of which 3 were protein-coding genes and 8 were lncRNA genes．It laid a foundation for further function- al verification and comprehensive analysis of the occurrence and development process of gastric cancer.