The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

Chronic graft-versus-host disease(cGVHD)is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation,with the incidence of 30％-70％.Unlike acute GVHD,cGVHD involves a large number of immune cells and cytokines in addition to T cell,which is activated abnormally by the donor,and cytokine storms,which characterized by infiltration of donor lymphocytes and damage to host target organ.Recent studies have further made progress in targeting related immune cells and cytokines.In this review,the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

Aim To investigate the effects of berberine(BBR)combined with 5'-n-ethylformamidoadenosine(NECA)on myocardial H9c2 and HL-1 cell damage induced by hypoxia/reoxygenation(H/R).Methods H9c2 and HL-1 cells were divided into the Control group,BBR group,NECA group,combined administra-tion group,H/R group,BBR+H/R group,NECA+H/R group,and combined administration+H/R group.CCK-8 was used to detect cell viability in each group.The TMRE kit was used to detect MMP.DCFH-DA was used to detect ROS content.The Mito SOX Red fluorescent probe was used to detect mitochondrial su-peroxide.The expressions of COX Ⅳ,Tom20,and Tim23 were detected by Western blot.The expression of COX Ⅳ and Tom20 genes was detected by qRT-PCR.Results In H9c2 cells,the cell viability and TMRE fluorescence intensity in the H/R group were significantly decreased compared with the Control group.The protein expressions of COX Ⅳ,Tom20,and Tim23,gene expressions of COX Ⅳ and Tom20,ROS,and mitochondrial superoxide contents were significant-ly increased.Compared with the H/R group,the cell viability of BBR and NECA were enhanced after ad-ministration alone.The contents of ROS and mitochon-drial superoxide were significantly decreased.In HL-1 cells,cell viability in the H/R group was significantly decreased compared with the Control group.The con-tents of ROS and mitochondrial superoxide were signifi-cantly increased.Compared with the H/R group,BBR and NECA alone and combined administration en-hanced cell viability.The contents of ROS and mito-chondrial superoxide were significantly decreased.Conclusion The administration of BBR and NECA a-lone or in combination can reduce the production of mi-tochondrial superoxide and cell ROS,thereby allevia-ting mitochondrial damage,alleviating oxidative stress damage,and ultimately reducing H/R-induced myocar-dial cell damage.

At the end of 2019, a new form of pneumonia disease known as the corona virus disease 2019 (COVID-19) rapidly spread throughout most provinces of China, and the total global number of COVID-19 cases has surpassed 500 000 by Mar. 27, 2020 (WHO, 2020). On Jan. 30, 2020, the World Health Organization (WHO) declared COVID-19 a global health emergency (WHO, 2020). COVID-19 causes most damage to the respiratory system, leading to pneumonia or breathing difficulties. The confirmed case fatality risk (cCFR) was estimated to be 5% to 8% (Jung et al., 2020). Besides physical pain, COVID-19 also induces psychological distress, with depression, anxiety, and stress affecting the general population, quarantined population, medical staff, and patients at different levels (Kang et al., 2020; Xiang et al., 2020). Previous research on patients in isolation wards highlighted the risk of depressed mood, fear, loneliness, frustration, excessive worries, and insomnia (Abad et al., 2010).
Adult ; Anxiety ; therapy ; Betacoronavirus ; China ; Coronavirus Infections ; psychology ; therapy ; Depression ; therapy ; Dialectical Behavior Therapy ; Female ; Humans ; Pandemics ; Pneumonia, Viral ; psychology ; therapy ; Postpartum Period ; Pregnancy ; Pregnant Women ; psychology

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective To observe the change of the relative concentration of oxygenated hemoglobin in the frontal cortex during cognitive processing in patients with post-stroke depression (PSD), and to discuss the neural mechanism and changes of working memory function of PSD preliminarily. Methods From February to August,2017,20 patients with PSD(PSD group)and 20 patients with non-depressive(con-trol group)were recruited.NIRSport portable functional near-infrared spectroscopy system was used to observe the change of the relative concentration of hemoglobin in the frontal cortex during the emotional face gender judgment task and"1-back"working memory task. Results Compared with the control group,the change of the relative concentration of oxygenated hemoglobin in the pre-frontal cortex was significantly lower after the negative emotion faces were presented in PSD group(t=3.872,P<0.001).In the implementation of the"1-back",the change of the relative concentration of oxygenated hemoglo-bin in the left prefrontal cortex was significantly lower in PSD group than in the control group(t=2.475,P<0.05), however,there was no significant difference in the change in the right prefrontal cortex between two groups(t=1.773,P=0.084). Conclusion The prefrontal cortex activity decrease in patients with PSD after the negative emotion faces were present-ed.The left prefrontal working memory function is impaired.The patients with PSD have disorder of oxygen me-tabolism in the prefrontal lobe.

Background: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism. Methods: Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX. Results: Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group. Conclusions This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.
Adolescent ; Animals ; Apoptosis ; genetics ; physiology ; Cell Line ; Female ; Flow Cytometry ; Glomerulosclerosis, Focal Segmental ; genetics ; Humans ; Immunohistochemistry ; Mice ; Mutation ; genetics ; Podocytes ; metabolism ; pathology ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; metabolism ; Ubiquinone ; analogs & derivatives ; genetics ; metabolism

Postpartum hemorrhage (PPH) is one of the most adverse obstetric outcomes.Our aim is to detect the risks of multilevel PPH in different cesarean section (CS) groups [including nulliparous CS with indications,nulliparous CS without indications,repeat cesarean (RC),vaginal birth after cesarean (VBAC),cesarean after vaginal birth (CAVB)].We conducted a retrospective cohort study,and the data on 127 145 women collected from January 2014 to May 2016 and from 35 tertiary hospitals in Shanxi province,China,were reviewed.Based on the measuring results of PPH,an ordered logistic regression model was used to analyze the adjusted PPH risks for each of the CS groups,and comparisons were drawn between them.Finally,a total of 99 066 nulliparous (77.92％) and 28 079 multiparous (22.08％) women were observed.The number of CS cases was 61 117,and the rate for CS was 48.07％.A total of 10 029 women did not show indications for CS and accounted for 16.41％ of the CS parturient,whereas 9103 women underwent a repeated cesarean,with a CS frequency of 14.89％.The number of VBAC cases was 989,whose rate was 9.88％ in prior CS women.The number (proportions) of PPH was 3658 (2.88％) in LI (PPH volume:≥900 and ＜1500 mL),520 (0.41％) in L2 (PPH volume:≥1500 and＜2100 mL),and 201 (0.16％) in L3 (PPH volume:≥2100 mL).The Ln (n=1,2,3,etc.) represented the increasing order of PPH severity.In the adjusted results,compared with spontaneous vaginal delivery (SVD) as the reference group,in the adjusted result for nulliparous,there was a decreased PPH risk in CS with indications (OR:2.32;CI:2.04-2.62),which was lower than that of CS without indications (OR:2.50;CI:2.01-2.96).The highest PPH risk in all subgroups (i.e.nulliparous and multiparous groups) was observed in the RC (OR:3.61;CI:3.16-4.17),which was nearly twice higher than that of the VBAC (OR:1.82;CI:1.33-2.52).CAVB (OR:1.03;CI:0.65-1.62) showed no significant difference with the reference group.Thus,we deemed that CS should be avoided in nulliparous pregnancies unless indicated,to prevent or reduce the rates for the use of RC or VBAC which are high risks of severe PPH to the parturient women.

Objective To investigate the effect of heart rate variability (HRV) biofeedback training on patients with three types of insom-nia disorder. Methods From June, 2016 to March, 2017, 17 patients in simple insomnia group, 19 patients in insomnia with anxiety group, and 19 patients in insomnia with depression group were included. All the patients received HRV biofeedback training and same medication (zolpidem tartrate, 10 mg every night). They were assessed with Pittsburgh Sleep Quality Index (PSQI), Symptom Checklist 90 (SCL-90), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and HRV parameters were tracked before and after training. Re-sults After training, the scores of PSQI, SCL-90, HAMA , HAMD and the ratio of low frequency (LF) and high frequency (HF) (LF/HF) de-creased in all groups (t>1.446, P<0.05). There was significant difference in PSQI among three groups (F=3.537, P=0.038). The D-values of the PSQI score and LF/HF before and after training were more in the insomnia with anxiety group and the insomnia with depression group than in the simple insomnia group (P<0.05), however, no significant difference was observed between the insomnia with anxiety group and the insomnia with depression group (P>0.05). Conclusion HRV biofeedback training could improve the symptoms of patients with three types of insomnia disorder, especially for those with anxiety or depression.

The paper was aimed to investigate the association of VDR polymorphisms with tacrolimus (FK506) concentration in Chinese renal transplant recipients. A total of 114 renal transplant recipients receiving tacrolimus were genotyped for VDR rs1540339 and rs2853559 by Agena Bioscience MassARRAY^® system and CYP3A5*3 by PCR-RFLP method. Trough concentrations of tacrolimus on day 7 after renal transplantation were collected from clinical data. Statistical analysis was performed with Spearman's correlation, Mann-Whitney U test and Kruskal-Wallis H test. The dose-adjusted concentration of tacrolimus in VDR rs2853559 GA and GG carriers were considerably higher than that of AA carriers. After stratification by CYP3A5*3 genotypes, VDR rs2853559 GA and GG carriers had a higher dose-adjusted tacrolimus concentration than that in AA carriers in CYP3A5 nonexpresser. CYP3A5*3 and VDR rs2853559 explained 45.6% variability of tacrolimus C₀/D. In CYP3A5 non-expressers, VDR rs2853559 explained 14.4% variability of tacrolimus C₀/D. The results illustrated that VDR rs2853559 polymorphisms was associated with tacrolimus concentrations, and the determination of this SNP may be useful for individualized medicine of tacrolimus.