One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective To explore the mechanism of lipid metabolism disorder promoting the progress of lung cancer based on the oxidized low density lipoprotein(ox-LDL)/human lectin-like oxidized low density lipopro-tein receptor 1(LOX-1)signaling pathway.Methods Eighty-one identified lung adenocarcinoma tissues with paired adjacent non-cancerous tissues(at least 5 cm away from the tumor)were collected from our hospital,and the expression of LOX-1 was detected by immunohistochemistry.LOX-1 was overexpressed in lung adenocarcinoma cell lines(A549 and H1299 cells).Cell invasion ability was measured by Transwell.Cells were treated with different concentrations of oxLDL,and cellular LOX-1 expression was investigated.Results LOX-1 staining in the tumor was significantly stronger than that in the non-cancerous tissue samples(99.4 vs.16.2 for median H score,P<0.001).High LOX-1 expression was significantly correlated with low survival(P<0.001).As compared with the patients without lymph node metastasis,those with lymph node metastasis had higher LOX-1 level(83.2 vs.121.1 for median H score,P<0.01).Overexpression of LOX-1 in lung cancer cells significantly promoted the number of invasive and metastatic cells(P<0.01).In addition,LOX-1 was an essential functional target for oxLDL-induced metastasis of lung cancer cells.Itatinib inhibited the metastasis of LOX-1 overexpressed A549 in vitro.Conclusions With an increase in oxLDL level,the expression of LOX-1 increases.Up-regulation of LOX-1 promotes metastasis of lung cancer,and its mechanism may be related to activation of the JAK1/STAT6 signaling pathway.

Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.

Objective To investigate the clinical effect of remimazolam combined with remifentanil in patients undergoing laryngoscope vocal cord surgery under general anesthesia.Methods A total of 180 patients undergoing laryngoscope vocal cord surgery under general anesthesia from January to August 2022,77 males and 103 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ were select-ed.The patients were divided into four groups using a random number table method:propofol group(group C),remimazolam 1.0 mg·kg-1·h-1 group(group R1),remimazolam 1.5 mg·kg-1·h-1 group(group R2),and remimazolam 2.0 mg·kg-1·h-1 group(group R3),45 patients in each group.Group C main-tained by intravenous infusion of propofol 5 mg·kg-1·h-1,groups R1,R2,and R3 were maintained by intravenous infusion of remimazolam 1.0,1.5,and 2.0 mg·kg-1·h-1,respectively.All patients were combined with remifentanil 0.2 μg·kg-1·min-1.HR,MAP,and BIS were recorded before anesthesia in-duction(T1),immediately after laryngoscope insertion(T2),immediately at the end of anesthesia mainte-nance(T3),and at tracheal extubation(T4).The onset time of sedation,awakening time,sedation-agita-tion score at extubation and Ramsay score 5 minutes after extubation were recorded.The intraoperative use of ephedrine and nitroglycerin were recorded.The number of injection pain and remedy sedations were recor-ded,the occurrence of adverse reactions such as nausea and vomiting,respiratory depression within 1 hour after extubation,and intraoperative awareness were recorded.Results Compared with group C,MAP at T3,BIS at T2 and T3 were significantly increased,MAP at T4 was significantly decreased,the onset time of sedation was significantly prolonged,the use of ephedrine and the incidence of injection pain were signifi-cantly decreased in group R1(P＜0.05),HR and MAP were significantly decreased at T2 and T4,MAP was significantly increased at T3,the onset time of sedation,awakening time,extubation time were signifi-cantly prolonged,the use of ephedrine and the incidence of injection pain were significantly reduced in group R2(P＜0.05),HR and MAP were significantly decreased at T2 and T4,the onset time of sedation,awakening time,extubation time were significantly prolonged,Ramsay score was significantly increased in group R3(P＜0.05).Compared with group R1,HR and MAP were significantly decreased at T2 and T4,BIS was significantly decreased at T2 and T3,the awakening time and extubation time were significantly pro-longed in group R2(P＜0.05),HR at T2 and T4,MAP at T2-T4,BIS at T2 and T3 were significantly de-creased,the awakening time and extubation time were significantly prolonged,Ramsay score was significant-ly increased in group R3(P＜0.05).Compared with group R2,MAP at T3 was significantly decreased and Ramsay score was significantly increased in group R3(P＜0.05).There were no significantly differences between the rates of nitroglycerin usage,rescue sedation,nausea and vomiting,and respiratory depression in the four groups.Conclusion Remimazolam can be safely used for anesthesia induction and maintenance in laryngoscope vocal cord surgery.The maintenance of remimazolam 1.5 mg·kg-1·h-1 combined with remifentanil can better maintain the hemodynamics stability during the surgery than remimazolam 1.0 and 2.0 mg·kg-1·h-1.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

OBJECTIVES: Urinary tract infection (UTI) is the most common infection complication after kidney transplantation, and the reports of the incidence vary greatly among different centers. This study aims to explore the risk factors for UTI after kidney transplantation with the donation from brain death (DBD) and the impact on graft function, thus to provide theoretical basis for comprehensive prevention and treatment of UTI after kidney transplantation. METHODS: The clinical and laboratory data of DBD kidney transplantation from January 2017 to December 2018 in Xiangya Hospital, Central South University were collected and retrospectively analyzed. Patients were assigned into an UTI group and a non-UTI group. The base line characteristics, post-transplant complications, and graft function were compared between the 2 groups. Multivariate logistic regression was used to analyze the risk factors for UTI. RESULTS: A total of 212 DBD kidney transplant recipients were enrolled in this study. UTI occurred in 44 (20.75%) patients after transplantation. The female, the time of indwelling catheter, and postoperative urinary fistula were independent risk factors for UTI after DBD kidney transplantation. A total of 19 strains of gram-positive bacteria, 12 strains of gram-negative bacteria , and 10 strains of fungi were isolated from the urine of 44 UTI patients. The UTI after kidney transplantation significantly increased time of hospital stay ( CONCLUSIONS UTI after DBD kidney transplantation transplantation affects the renal function at 3 months and increases the patient's economic burden.
Brain Death ; Female ; Humans ; Kidney Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Urinary Tract Infections/etiology*

AIM: To compare the bioavailability of norfloxacin tablets produced by Zhejiang Pharmaceutical Co., Ltd with the original product BACCIDAL, and to evaluate bioequivalence of two formulations, a randomized, open, two-cycle, self-crossing trial in healthy Chinese population was designed. METHODS: Under fasting and fed conditions, healthy volunteers were given a single dose of norfloxacin test or reference tablets for 100 mg. Liquid chromatography-mass spectrometry (LC-MS/MS) method were used to determine drug concentration in the plasma taken at different time points before and after dosing. Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software. RESULTS: A total of 28 healthy volunteers were enrolled and completed the fasting test. The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: C

Objective: To investigate the effects of thrombopoietin (TPO) on proliferation and collagen synthesis in pulmonary fibro-blasts induced by TGFβ1. Methods: Cultured human embryonic lung fibroblasts (HFLs) were treated with recombinant human TGF-β1 to induce myofibroblast differentiation. Different concentrations of recombinant human TPO were applied individually or in combina-tion. Cell proliferation rate was determined using the CCK8 assay. Q-PCR and immunofluorescence assay were employed to examine the mRNA and protein expression of α-smooth muscle actin (αSMA) and type I collagen (COL1)A2. Results: TGFβ1 treatment induced HFL transdifferentiation to myofibroblasts was determined by the expression of αSMA, a myofibroblast-specific marker. Cell prolifera-tion increased during the induction. COL1 gene and protein expression were upregulated by TGFβ1 induction (P<0.05). The TGFβ1-in-duced mRNA and protein expression of αSMA and COL1A2 was decreased by TPO treatment (P<0.05), as determined by reverse tran-scription quantitative polymerase chain reaction and immunofluorescence analysis, respectively. The inhibitory rate showed a dose de-pendent effect within a certain TPO concentration range. The CCK8 assay demonstrated that TPO downregulated the TGFβ1-induced proliferation (P<0.05). Furthermore, the expression of heme oxygenase-1 (HO-1) was downregulated in TGFβ1-induced lung fibro-blasts, and these effects were attenuated by TPO administration (P<0.05). Conclusions: TPO can inhibit the TGFβ1-induced prolifera-tion and differentiation of human lung fibroblasts. These effects may be mediated in part by HO-1-related signaling pathways.