Publications by authors named "Ping Zhang"

3,064 Publications

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Reconstruction of Large Area of Deep Wound in the Foot and Ankle with Chimeric Anterolateral Thigh Perforator Flap.

Orthop Surg 2021 Jun 17. Epub 2021 Jun 17.

Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle.

Methods: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded.

Results: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up.

Conclusion: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.
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http://dx.doi.org/10.1111/os.13046DOI Listing
June 2021

Deep-learning models for the detection and incidence prediction of chronic kidney disease and type 2 diabetes from retinal fundus images.

Nat Biomed Eng 2021 Jun 15;5(6):533-545. Epub 2021 Jun 15.

Peking University Third Affiliated Hospital, Beijing, China.

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min per 1.73 m and 0.65-1.1 mmol l, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.
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http://dx.doi.org/10.1038/s41551-021-00745-6DOI Listing
June 2021

A new soft-matter material with old chemistry: Passerini multicomponent polymerization-induced assembly of AIE-active double-helical polymers with rapid visible-light degradability.

Chem Sci 2020 Jul 15;11(31):8224-8230. Epub 2020 Jul 15.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University Xi'an China

Mimicking the superstructures and functions of natural chiral materials is beneficial to understand specific biological activities in living organisms and broaden applications in the fields of chemistry and materials sciences. However, it is still a great challenge to construct water-soluble, double-helical polymers with multiple responsiveness. Herein, we report for the first time a straightforward, general strategy to address this issue by taking advantage of Passerini multicomponent polymerization-induced assembly (PMPIA). The polymerization-induced generation of supramolecular interactions in chiral α-acyloxy amides drives the assembly of polymers and improves their stability in various solvents. This double-helical polymer is sensitive to metal ions, temperature, pH, and solvents, making both the superstructure and the AIE effect reversibly adjustable. Meanwhile, the hydrogen-bonding-assisted cyclization of photolabile α-acyloxy amides accelerates the degradation of helical polymers under visible-light irradiation. It is anticipated that this novel PMPIA strategy opens new horizons to inspire the design of advanced chiral/helical polymers with multiple functions.
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http://dx.doi.org/10.1039/d0sc02729dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163360PMC
July 2020

Neuroprotective effects of microRNA-211-5p on chronic stress-induced neuronal apoptosis and depression-like behaviours.

J Cell Mol Med 2021 Jun 13. Epub 2021 Jun 13.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Findings from recent studies have revealed that microRNAs (miRNAs) are related to numerous neurological disorders. However, whether miRNAs regulate neuronal anomalies involved in the pathogenesis of depression remain unclear. In the present study, we screened miRNA expression profiles in the CA1 hippocampus of a rat model of depression and found that a specific miRNA, microRNA-211-5p, was significantly down-regulated in depressed rats. When miR-211-5p was up-regulated in these rats, neuronal apoptosis within the CA1 area was suppressed, effects which were accompanied with an amelioration of depression-like behaviours in these rats. These neuroprotective effects of miR-211-5p in depressed rats appear to result through suppression of the Dyrk1A/ASK1/JNK signalling pathway within the CA1 area. In further support of this proposal are the findings that knock-down of miR-211-5p within the CA1 area of normal rats activated the Dyrk1A/ASK1/JNK pathway, resulting in the promotion of neuronal apoptosis and display of depression-like behaviours in these rats. Taken together, these results demonstrate that deficits in miR-211-5p contribute to neuronal apoptosis and thus depression-like behaviours in rats. Therefore, the miR-211-5p/Dyrk1A pathway may be critically involved in the pathogenesis of depression and serve as a potential therapeutic target for the treatment of depression.
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http://dx.doi.org/10.1111/jcmm.16716DOI Listing
June 2021

Capturing the grouping and compactness of high-level semantic feature for saliency detection.

Neural Netw 2021 Apr 24;142:351-362. Epub 2021 Apr 24.

School of Physics Electronic Engineering, Nanyang Normal University, Nanyang 473061, China.

Saliency detection is an important and challenging research topic due to the variety and complexity of the background and saliency regions. In this paper, we present a novel unsupervised saliency detection approach by exploiting the grouping and compactness characteristics of the high-level semantic features. First, for the high-level semantic feature, the elastic net based hypergraph model is adopted to discover the group structure relationships of salient regional points, and the calculation of the spatial distribution is constructed to detect the compactness of the saliency regions. Next, the grouping-based and compactness-based saliency maps are improved by a propagation algorithm. The propagation process uses an enhanced similarity matrix, which fuses the low-level deep feature and the high-level semantic feature through cross diffusion. Results on four benchmark datasets with pixel-wise accurate labeling demonstrate the effectiveness of the proposed method. Particularly, the proposed unsupervised method achieves competitive performance with deep learning-based methods.
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http://dx.doi.org/10.1016/j.neunet.2021.04.028DOI Listing
April 2021

CMV exposure drives long-term CD57+ CD4 memory T cell inflation following allogeneic stem cell transplant.

Blood 2021 Jun 3. Epub 2021 Jun 3.

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States.

Donor and recipient cytomegalovirus (CMV) serostatus correlate with transplant related mortality that is associated with reduced survival following allogeneic stem cell transplant (SCT). Prior epidemiologic studies have suggested that CMV seronegative recipients (R-) receiving a CMV seropositive graft (D+) experience inferior outcomes compared to other serostatus combinations, an observation that appears independent of viral reactivation. We therefore investigated the hypothesis that prior donor CMV exposure irreversibly modifies immunologic function after SCT. We identified a CD4+/CD57+/CD27- T cell subset that was differentially expressed between D+ and D- transplants and validated results with 120 patient samples. This T cell subset represents an average of 2.9% (D-/R-), 18% (D-/R+), 12% (D+/R-), and 19.6% (D+/R+) (p<0.0001) of the total CD4+ T cell compartment and stably persists for at least several years post-SCT. Even in the absence of CMV reactivation post-SCT, D+/R- transplants displayed a significant enrichment of these cells compared to D-/R- transplants (p=0.0078). These are effector memory cells (CCR7-/ CD45RA+/-) that express T-bet, EOMES, granzyme B, secrete Th1 cytokines, and are enriched in CMV-specific T cells. These cells are associated with decreased T cell receptor diversity (p<0.0001) and reduced proportions of major histocompatibility class II expressing classical monocytes (p<0.0001), myeloid (p=0.024), and plasmacytoid dendritic cells (p=0.0014). These data describe a highly expanded CD4+ T cell population and putative mechanisms by which prior donor or recipient CMV exposure may create a lasting immunologic imprint following SCT, providing a rationale for using D- grafts for R- transplant recipients.
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http://dx.doi.org/10.1182/blood.2020009492DOI Listing
June 2021

A Guide to Nucleic Acid Vaccines in the Prevention and Treatment of Infectious Diseases and Cancers: From Basic Principles to Current Applications.

Front Cell Dev Biol 2021 25;9:633776. Epub 2021 May 25.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Faced with the challenges posed by infectious diseases and cancer, nucleic acid vaccines present excellent prospects in clinical applications. Compared with traditional vaccines, nucleic acid vaccines have the characteristics of high efficiency and low cost. Therefore, nucleic acid vaccines have potential advantages in disease prevention and treatment. However, the low immunogenicity and instability of nucleic acid vaccines have limited their development. Therefore, a large number of studies have been conducted to improve their immunogenicity and stability by improving delivery methods, thereby supporting progress and development for clinical applications. This article mainly reviews the advantages, disadvantages, mechanisms, delivery methods, and clinical applications of nucleic acid vaccines.
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http://dx.doi.org/10.3389/fcell.2021.633776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185206PMC
May 2021

Physical and Psychosocial Responses to COVID-19 in Chinese Frontline Nurses: A Cross-Sectional Study.

J Psychosoc Nurs Ment Health Serv 2021 Jun 1:1-8. Epub 2021 Jun 1.

Using Gordon's Functional Health Pattern Model, the current cross-sectional study aimed to survey physical and psychosocial responses to the coronavirus disease 2019 (COVID-19) pandemic among Chinese frontline nurses and to identify the most vulnerable groups for future reference and interventions. A self-administered online questionnaire was used to collect demographic data and stress reactions of 115 Chinese frontline nurses. The 52-item version of Gordon's Functional Health Questionnaire was used to evaluate physical, psychological, and social effects of the COVID-19 pandemic among participants. The most prevalent problems were reported in the psychological aspect, where respondents referred to altered self-image due to constant use of masks (87.8%), excessive attention to clinical signs of COVID-19 (59.2%), depression (54%), forgetfulness (40.9%), and anxiety (39.1%). The most vulnerable nurses were those who were younger, had a chronic disease, and were divorced. [(xx), xx-xx.].
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http://dx.doi.org/10.3928/02793695-20210426-01DOI Listing
June 2021

A clinical study of lyophilized intravenous human immunoglobulin containing high-titer cytomegalovirus-neutralizing antibody for the treatment of cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation.

Ann Palliat Med 2021 May;10(5):5533-5540

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Background: Cytomegalovirus (CMV) infection increases the risk of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, some patients do not respond to ganciclovir (GCV) or foscarnet sodium. Lyophilized intravenous human immunoglobulin containing high-titer CMV-neutralizing antibody (CMV-IVIG) is another option to further improve treatment safety and efficacy. This study was designed to evaluate the efficacy of the combination of CMV-IVIG with traditional antiviral drugs (GCV or foscarnet sodium) at different time points for the treatment of post-allo-HSCT CMV viremia and to determine the clinical value of CMV-IVIG as a preemptive treatment strategy.

Methods: The clinical data of 73 patients who received allo-HSCT and concurrent CMV-IVIG to treat post-allo-HSCT CMV viremia at our hospital between January and September 2020 were retrospectively analyzed. The patients were divided into two groups based on the total dose of antithymocyte globulin (ATG) used in the pretransplant preconditioning regimen, i.e., the low-dose ATG group (rabbit ATG ≤6 mg/kg, porcine ATG ≤40 mg/kg) (n=19) and the high-dose ATG group (rabbit ATG >6 mg/kg, porcine ATG >40 mg/kg) (n=54). Real-time quantitative polymerase chain reaction (RQ-PCR) was performed to measure the peripheral CMV-DNA level. Patients with CMV viremia (CMV-DNA >1,000 copies/mL) received concurrent CMV-IVIG therapy [early (within 3 days after the diagnosis of CMV viremia) or late (after 3 days)]. The CMV-DNA conversion rate, the median time of CMV-DNA conversion, and the two-week response rate and reactivation rate were analyzed for different ATG doses and different time points of CMV-IVIG use.

Results: The overall response rate to CMV-IVIG combined with traditional anti-CMV drugs was 100%. Early use of CMV-IVIG significantly reduced the median time of CMV-DNA conversion (14 vs. 21 days, P=0.000), especially in the high-dose ATG group (14 vs. 23 days, P=0.000).

Conclusions: For patients with post-allo-HSCT CMV viremia, early use of CMV-IVIG effectively accelerates CMV-DNA conversion and peripheral CMV clearance, significantly improves the two-week response rate, and reduces the two-week reactivation rate. These effects are more pronounced in the high-dose ATG group.
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http://dx.doi.org/10.21037/apm-21-1069DOI Listing
May 2021

NHBS-Net: A Feature Fusion Attention Network for Ultrasound Neonatal Hip Bone Segmentation.

IEEE Trans Med Imaging 2021 Jun 9;PP. Epub 2021 Jun 9.

Ultrasound is a widely used technology for diagnosing developmental dysplasia of the hip (DDH) because it does not use radiation. Due to its low cost and convenience, 2-D ultrasound is still the most common examination in DDH diagnosis. In clinical usage, the complexity of both ultrasound image standardization and measurement leads to a high error rate for sonographers. The automatic segmentation results of key structures in the hip joint can be used to develop a standard plane detection method that helps sonographers decrease the error rate. However, current automatic segmentation methods still face challenges in robustness and accuracy. Thus, we propose a neonatal hip bone segmentation network (NHBS-Net) for the first time for the segmentation of seven key structures. We design three improvements, an enhanced dual attention module, a two-class feature fusion module, and a coordinate convolution output head, to help segment different structures. Compared with current state-of-the-art networks, NHBS-Net gains outstanding performance accuracy and generalizability, as shown in the experiments. Additionally, image standardization is a common need in ultrasonography. The ability of segmentation-based standard plane detection is tested on a 50-image standard dataset. The experiments show that our method can help healthcare workers decrease their error rate from 6%-10% to 2%. In addition, the segmentation performance in another ultrasound dataset (fetal heart) demonstrates the ability of our network.
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http://dx.doi.org/10.1109/TMI.2021.3087857DOI Listing
June 2021

Helicobacter pylori reinfection and its risk factors after initial eradication: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 May;100(19):e25949

Jiangxi University of Traditional Chinese Medicine.

Background: Helicobacter pylori (H pylori) infection is a common health problem, which is closely related to peptic ulcers, gastric cancer, and extragastric diseases. Drugs can successfully eradicate it. However, the recurrence of H pylori often occurs after initial eradication. To confirm the global incidence of H pylori reinfection and systematically evaluate its risk factors.

Methods: We will search for the relevant literature through Chinese and English databases, with the retrieval deadline being November 2021. Databases include PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database. Stata14.0 will be used to conduct this systematic review. The preferred reporting items for systematic reviews and meta-analysis protocols statements are followed in this protocol, and the PRISMA statement will be followed in the completed systematic review.

Results: The results will be published in a peer-reviewed journal.

Conclusions: This systematic review will provide evidence regarding the rate of H pylori reinfection and its risk factors after successful eradication. It can guide the management of patients with H pylori infection.
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http://dx.doi.org/10.1097/MD.0000000000025949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133036PMC
May 2021

Identification of 16SrXXX-A Phytoplasma Associated with Salt cedar (Tamarix chinensis Lour.) witches'-broom (SCWB) in Southern Xinjiang of China.

Plant Dis 2021 Jun 8. Epub 2021 Jun 8.

Tarim University, 12483, Plant Science, Aral, Xinjiang, China;

Salt cedar is an ornamental shrub/moderate tree species native to Asia and East Europe, and grows in salt-alkali soil, desert and other dry areas, which plays an important role in wind prevention and sand fixation as well as maintaining ecological balance. Salt cedar witches'-broom (SCWB), which was extremely pernicious to Salt cedar. It was first observed and reported in Xi'an, China in 2005 (Zhao et al.2005). Witches' broom symptoms were observed on 20 out of 150 (13.3%) salt plants surveyed from the Alar region and 10 out of 86 (11.6%) plants from the Akesu region in southern of Xinjiang in May 2020. The damaged plants compared with asymptomatic plants (Fig.1A), the major symptoms included branches clustered, intersegment shorten and coarsen, giving rise to the formation of clusters (Fig.1B). Total plant DNA was extracted from phloem tissues with asymptomatic symptoms and phloem tissues with witches'-broom symptoms by a CTAB-based DNA extraction method (Green et al.1999). The 16S rRNA gene and the phytoplasma universal primers P1/P7 and rpF1/rpR1 of the rp (ribosomal protein) gene were used for Polymerase chain reaction (PCR) amplification by using the extracted plant total DNA as the template. The PCR product was used as the template and the R16F2n/R16R2 prmer was used for nested PCR amplification of the 16S rRNA gene after the amplification was completed. The results show that no product was obtained in asymptomatic plants. When DNA samples from witches'-broom symptomatic plants were used as templates, fragments with lengths 1219 bp and 1174 bp, corresponding to 16S rRNA gene and rp gene, were obtained. 16S rRNA gene was sequenced and deposited in GenBank under accession number MW447513. BLAST analysis revealed that the partial 16S rRNA sequence of the phytoplasma associated with P. aphylla witches' broom showed highest sequence identity (99.67%) to salt cedar witches' broom phytoplasma, 'Candidatus Phytoplasma tamaricis' (Accession Number: FJ432664). Phylogenetic and molecular evolutionary analyses were conducted using MEGA-X (Kumar et al., 2018). Results showed taht the SCWB and 16S rXXX group's'Candidatus Phytoplasma tamaricis', (GenBank accession: FJ432664) have the highest affinity (Fig.2A). A virtual restriction fragment length polymorphism(RFLP) was done to determinethe subgroup ( Zhao et al. 2009). The 16S rDNA sequence from the Tamarix chinensis plant showed 99.3% similarity with that of the "Candidatus Phytoplasma tamaricis" reference strain (GenBank accession: FJ432664), suggesting that the phytoplasma in this study belongs to "Candidatus Phytoplasma tamaricis"-related strain. Therefore, it can be stated that SCWB belongs to the 16S rXXX group. The partial rp sequences only shared 84.74% sequence similarity with that of 'Candidatus Phytoplasma prunorum' (MG383523) of Apple proliferation group, a known subgroup 16S rX. Blast analysis based on the partial rp sequences showed that it shares less than 90% similarity with that of any known phytoplasma (Fig 2B), we suspect that this is due to a lack of sequenced rp gene sequences for the 16S rXXX group. To our knowledge, this is the first report of Salt Cedar Witches' Broom phytoplasma in Xinjiang province, China. As a consequence, we guess the SCWB phytoplasma rp gene belongs to 16S rXXX-rp group, which is also the first report about the 16SrXXX-rp group. Because SCWB1 is the only strain in the 16S rXXX group, and it is the representative strain of the 16S rXXX-A subgroup (Zhao et al. 2009). So, the SCWB disease we found in southern Xinjiang belongs to the 16S rXXX-A subgroup.
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http://dx.doi.org/10.1094/PDIS-03-21-0555-PDNDOI Listing
June 2021

Design and Feasibility Tests of a Lightweight Soft Gripper for Compliant and Flexible Envelope Grasping.

Soft Robot 2021 Jun 7. Epub 2021 Jun 7.

Key Laboratory of Ocean Energy Utilization and Energy Conservation of Ministry of Education, Dalian University of Technology, Dalian, China.

A lightweight soft gripper for envelope grasping is proposed. The main component of the gripper is a spherical latex superelastic membrane whose material properties allow a grabbing function to be realized. The grasping process includes the expansion and tightening of the membrane, and it does not require a constant supply of energy. The geometric relationship between the actuator and the target object are analyzed, from which a gripping force model is deduced to estimate the grasping ability. A test-rig was designed to verify the gripping force model experimentally. The gripper can inherently realize shape adaptability and safety. It is easy to manipulate and control for beginners. Moreover, an actuator of only 50 g can grasp and lift various objects, including fragile and irregularly shaped items with a maximum mass >650 g.
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http://dx.doi.org/10.1089/soro.2020.0156DOI Listing
June 2021

Genome-Wide Screen and Validation of Microglia Pro-Inflammatory Mediators in Stroke.

Aging Dis 2021 Jun 1;12(3):786-800. Epub 2021 Jun 1.

1Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Stroke activates microglia pro-inflammatory response that not only induces the early neuronal injuries but also causes the secondary brain infarction. Yet, the underlying mechanisms for how microglia become activated in stroke are still unknown. Here, using the next-generation of RNA sequencing we find a total of 778 genes increasingly expressed in brain of stroke mice. Of these, we identified Hmgb2 as a microglia pro-inflammatory mediator by promoting the transcription of Ctss. Inhibition of either Hmgb2 or Ctss blocks microglia pro-inflammatory response and protects against brain damages and improves the neurological functions of stroke mice. This study uncovers Hmgb2 and Ctss as the major microglia inflammatory response mediators in stroke and hence warrants the promising targets for stroke therapies.
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http://dx.doi.org/10.14336/AD.2020.0926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139211PMC
June 2021

PI3K/AKT pathway mediates the antidepressant- and anxiolytic-like roles of hydrogen sulfide in streptozotocin-induced diabetic rats via promoting hippocampal neurogenesis.

Neurotoxicology 2021 Jun 1;85:201-208. Epub 2021 Jun 1.

Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, PR China. Electronic address:

We have previously demonstrated that hydrogen sulfide (HS), the third endogenous gasotransmitter, ameliorates the depression- and anxiety-like behaviors in diabetic rats, but the underlying mechanism remains unclear. The present was aimed to investigate whether the hippocampal phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway mediates HS-ameliorated depression- and anxiety-like behaviors in diabetic rats by improving the hippocampal neurogenesis. The depression-like behaviors were examined by Tail suspension test (TST), the anxiety-like behaviors were examined by Elevated plus maze test (EPM), and the locomotor activity was detected by Open Field Test (OFT). The expressions of doublecortin (DCX), neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), p-AKT, and AKT in the hippocampus were determined by Western blot analysis. Results showed that NaHS, a donor of exogenous HS, not only activated the hippocampal PI3K/AKT pathway, as evidenced by the increase of phosphorylated AKT, but also favorably reversed streptozotocin (STZ)-disturbed hippocampal neurogenesis, as evidenced by the increases in the expressions of DCX and NeuN as well as the decrease in the expression of GFAP in the hippocampus of STZ-induced diabetic rats. Furthermore, inhibited PI3K/AKT pathway by LY294002 significantly abolished HS-exerted the improvement of hippocampal neurogenesis and the antidepressant- and anxiolytic-like effects in the STZ-induced diabetic rats. Taken together, these results uncover that the activation of hippocampal PI3K/AKT pathway plays an important role to restore hippocampal neurogenesis and subsequently to mediate the antidepressant- and anxiolytic-like roles of HS in STZ-induced diabetic rats and enhance our understanding of the robustness of HS as a therapeutic strategy for treatment of depression in diabetes mellitus.
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http://dx.doi.org/10.1016/j.neuro.2021.05.016DOI Listing
June 2021

Loss of phosphatidylserine flippase β-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis.

Dis Model Mech 2021 Jun 3. Epub 2021 Jun 3.

Health Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China.

Phosphatidylserine (PS) is asymmetrically concentrated in the cytoplasmic leaflet of eukaryotic cell plasma membranes. This asymmetry is regulated by a group of P4 ATPases (named PS flippases) and its β-subunit TMEM30A. The disruption of PS flippase leads to severe human diseases. Tmem30a is essential in the mouse retina, cerebellum and liver. However, the role of Tmem30a in the kidney, where it is highly expressed, remains unclear. Podocytes in the glomerulus form a branched interdigitating filtration barrier that can prevent the traversing of large cellular elements and macromolecules from the blood into the urinary space. Damage to podocytes can disrupt the filtration barrier and lead to proteinuria and podocytopathy, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and diabetic nephropathy. We observed reduced TMEM30A expression in patients with minimal change disease and membranous nephropathy, indicating potential roles of TMEM30A in podocytopathy. To investigate the role of Tmem30a in the kidney, we generated a podocyte-specific Tmem30a knockout (KO) mouse model using the NPHS2-Cre line. Tmem30a KO mice displayed albuminuria, podocyte degeneration, mesangial cell proliferation with prominent extracellular matrix accumulation and eventual progression to focal segmental glomerulosclerosis (FSGS). Our data demonstrate a critical role of Tmem30a in maintaining podocyte survival and glomerular filtration barrier integrity. Understanding the dynamic regulation of the PS distribution in the glomerulus provides a unique perspective to pinpoint the mechanism of podocyte damage and potential therapeutic targets.
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http://dx.doi.org/10.1242/dmm.048777DOI Listing
June 2021

Anti-allergic actions of a Chinese patent medicine, huoxiangzhengqi oral liquid, in RBL-2H3 cells and in mice.

Pharm Biol 2021 Dec;59(1):672-682

Chongqing Academy of Chinese Materia Medica, Chongqing, PR China.

Context: Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects.

Objective: The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL.

Materials And Methods: IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL) . The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c mice (5 mice/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days.

Results: HXZQ-OL not only inhibited degranulation of mast cells (IC, 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC, 171.4 μg/mL), TNF-α (IC, 88.4 μg/mL), LTC4 (IC, 52.9 μg/mL) and PGD2 (IC, 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in mice.

Conclusions: HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.
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http://dx.doi.org/10.1080/13880209.2021.1928242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183508PMC
December 2021

Study on Omentin-1 and miR-502-3p in osteoporotic fracture.

J Musculoskelet Neuronal Interact 2021 Jun;21(2):308-316

Huangdao District Central Hospital, Shandong Province, China.

Objectives: To explore the expression and correlation of Omentin-1 and miR-502-3p in serum of patients with osteoporotic fracture (OPF).

Methods: Sixty OPF patients diagnosed and treated in our hospital from June 2018 to December 2019 were included in group A. Fifty-six osteoporosis patients without fractures were included in group B. Omentin-1 and miR-502-3p levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qRT-PCR). Their predictive value for diagnostic efficiency was assessed by ROC curve. Spearman's rank correlation test was used for correlation analysis. The risk factors related to the prognosis of OPF were analyzed by Logistic univariate and multivariate analysis.

Results: The expression of Omentin-1 and miR-502-3p in group A was markedly lower than in group B (P<0.001). Spearman correlation analysis showed that in OPF, there was a negative correlation between serum Omentin-1 and TNF-α (r=0.8579, P<0.001), a negative correlation between serum miR-502-3p and TNF-α (r= 0.8653, P<0.001), and a positive correlation between serum Omentin-1 and miR-502-3p (r= 0.8764, P<0.001).

Conclusions: Omentin-1 and miR-502-3p were down-regulated in serum of patients with OPF, both of which could be used as potential biomarkers for the diagnosis and disease evaluation of OPF.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185270PMC
June 2021

Correction to: The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China.

BMC Med Genomics 2021 May 31;14(1):143. Epub 2021 May 31.

Department of Nephrology and Institute of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, 610072, China.

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http://dx.doi.org/10.1186/s12920-021-00992-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167973PMC
May 2021

MGRL: Predicting Drug-Disease Associations Based on Multi-Graph Representation Learning.

Front Genet 2021 8;12:657182. Epub 2021 Apr 8.

The Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Ürümqi, China.

Drug repositioning is an application-based solution based on mining existing drugs to find new targets, quickly discovering new drug-disease associations, and reducing the risk of drug discovery in traditional medicine and biology. Therefore, it is of great significance to design a computational model with high efficiency and accuracy. In this paper, we propose a novel computational method MGRL to predict drug-disease associations based on multi-graph representation learning. More specifically, MGRL first uses the graph convolution network to learn the graph representation of drugs and diseases from their self-attributes. Then, the graph embedding algorithm is used to represent the relationships between drugs and diseases. Finally, the two kinds of graph representation learning features were put into the random forest classifier for training. To the best of our knowledge, this is the first work to construct a multi-graph to extract the characteristics of drugs and diseases to predict drug-disease associations. The experiments show that the MGRL can achieve a higher AUC of 0.8506 based on five-fold cross-validation, which is significantly better than other existing methods. Case study results show the reliability of the proposed method, which is of great significance for practical applications.
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http://dx.doi.org/10.3389/fgene.2021.657182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153989PMC
April 2021

Diagnostic Value of Combined Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Diffusion Tensor Imaging in Predicting Parametrial Infiltration in Cervical Cancer.

Contrast Media Mol Imaging 2021 11;2021:6651070. Epub 2021 May 11.

Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, China.

Objective: This study sought to determine the diagnostic value of combined intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) in predicting parametrial infiltration (PMI) in patients with cervical cancer.

Materials And Methods: We enrolled 65 patients with cervical cancer confirmed by radical hysterectomy (25 PMI-negative and 40 PMI-positive) who underwent IVIM and DTI pretreatment. The parameters of IVIM (ADC, D, D  , and f) and DTI (average diffusion coefficient (DCavg) and fractional anisotropy (FA)) were recorded by two observers. All parameter differences were tested, and the receiver operating characteristic (ROC) curves were generated to estimate the diagnostic performance of significant metrics and their combinations.

Results: Compared to the PMI-negative group, the PMI-positive group had significantly lower D (0.632 ± 0.017 0.773 ± 0.024, < 0.001) and lower FA (0.073 ± 0.002 0.085 ± 0.003, =0.003). The area under the ROC curve (AUC) of D and FA was 0.801 and 0.726, respectively, and the combination of D and FA improved the AUC to 0.931, with a sensitivity and specificity of 80.0% and 97.5%, respectively.

Conclusion: D and FA values could be used to help diagnose PMI in patients with cervical cancer. The combination of IVIM and DTI was more valuable than either option alone.
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http://dx.doi.org/10.1155/2021/6651070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131167PMC
May 2021

A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer.

Int J Biol Markers 2021 May 31:1724600821992356. Epub 2021 May 31.

Department of Gynecology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China.

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors.

Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled.

Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy (<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975.

Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.
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http://dx.doi.org/10.1177/1724600821992356DOI Listing
May 2021

Organochlorine Pesticide Dieldrin Suppresses Cellular Interferon-related Antiviral Gene Expression.

Toxicol Sci 2021 May 29. Epub 2021 May 29.

Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, FL, USA.

Organochlorine pesticides (OCPs) are persistent pollutants linked to diverse adverse health outcomes. Environmental exposure to OCPs has been suggested to negatively impact the immune system but their effects on cellular antiviral responses remain unknown. Transcriptomic analysis of N27 rat dopaminergic neuronal cells unexpectedly detected high level expression of genes in the interferon-related anti-viral response pathways including the interferon-induced protein with tetratricopeptide repeats 1 and 2 (Ifit1/2) and the MX Dynamin Like GTPases Mx1 and Mx2. Interestingly, treatment of N27 cells with dieldrin markedly downregulated the expression of many of these genes. Dieldrin exterted a similar effect in inhibiting IFIT2 and MX1 gene expression in human human SH-SY5Y neuronal cells induced by an RNA viral mimic, polyinosinic:polycytidylic acid (poly I:C) and IFIT2/3 gene expression in human pulmonary epithelial cells exposed to human influenza H1N1 virus. Mechanistically, dieldrin induced a rapid rise in levels of intracellular reactive oxygen species (iROS) and a decrease in intracellular glutathione levels in in SH-SY5Y cells. Treatment with N-acetylcysteine, an antioxidant and glutathione biosynthesis precursor, effectively blocked both dieldrin-induced increases in iROS and its inhibition of poly I:C-induced upregulation of IFIT and MX gene expression, suggesting a role for intracellular oxidative status in dieldrin's modulation of anti-viral gene expression. This study demonstrates that dieldrin modulates key genes of the cellular innate immune responses that are normally involved in the host's cellular defense against viral infections. Our findings have potential relevance to understanding the organismal effects of environmentally persistent organochlorine contaminants on the mammalian cellular immune system.
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http://dx.doi.org/10.1093/toxsci/kfab064DOI Listing
May 2021

NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases.

J Transl Autoimmun 2021 6;4:100103. Epub 2021 May 6.

Nektar Therapeutics, 455 Mission Bay Boulevard South, San Francisco, CA, 94158, USA.

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, vo and pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus. NKTR-358 demonstrated decreased affinity for IL-2Rα, IL-2Rβ, and IL-2Rαβ compared with recombinant human IL-2 (rhIL-2). A single dose of NKTR-358 in cynomolgus monkeys produced a greater than 15-fold increase in regulatory T-cells, and the increase lasted until day 14, while daily rhIL-2 administration for 5 days only elicited a 3-fold increase, which lasted until day 7. Repeated dosing of NKTR-358 over 6 months in cynomolgus monkeys elicited cyclical, robust increases in regulatory T-cells with no loss in drug activity over the course of treatment. Regulatory T-cells isolated from NKTR-358-treated mice displayed a sustained, higher suppression of conventional T-cell proliferation than regulatory T-cells isolated from vehicle-treated mice. NKTR-358 treatment in a mouse model (MRL/MpJ-Fas) of systemic lupus erythematosus for 12 weeks maintained elevated regulatory T-cells for the treatment duration and ameliorated disease progression. Together, these results suggest that NKTR-358 has the ability to elicit sustained and preferential proliferation and activation of regulatory T-cells without corresponding effects on conventional T-cells, with improved pharmacokinetics compared with rhIL-2.
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http://dx.doi.org/10.1016/j.jtauto.2021.100103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141531PMC
May 2021

Ginsenoside Rg3 suppresses ovarian cancer cell proliferation and invasion by inhibiting the expression of lncRNA H19.

Acta Biochim Pol 2021 May 26. Epub 2021 May 26.

1Department of Gynecologic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Gongshu District, Hangzhou City, Zhejiang Province, 310000, China; 2Institute of Cancer and Basic Medicine, IBMC, Chinese Academy of Sciences, China.

Ovarian cancer (OC) is the most malignant disease of the female reproductive system and accounts for a large proportion of gynecological cancer-related deaths. Emerging evidence has indicated that ginsenoside Rg3, one of the tetracyclic triterpenoid saponins in ginseng, plays crucial roles in regulating cancer progression, yet its role and mechanisms in regulating the proliferation and invasion of OC are still elusive. In this study, the cell viability, proliferation, migration and invasion of OC were assessed by using methyl thiazol tetrazolium (MTT), colony formation, wound healing and Transwell assays, respectively. The protein levels of E-cadherin and N-cadherin were analyzed by Western blot assay. The expression of long noncoding RNA (lncRNA) H19 was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The results revealed that ginsenoside Rg3 significantly inhibited the viability of OC cells (SKOV3 and A2780) in a concentration‑dependent manner. Ginsenoside Rg3 (50 μg/ml) had almost no significant effect on the activity of human ovarian epithelial cells (HOSEpiCs). Thus, this dose was selected for the subsequent experiments. Furthermore, Rg3 markedly decreased the colony formation, migration and invasion of OC cells. In addition, the expression of N-cadherin was downregulated, and the expression of E-cadherin was upregulated with Rg3 treatment. Moreover, lncRNA H19 was upregulated in OC cells, and Rg3 negatively regulated H19 expression in a concentration-dependent manner. In terms of the mechanism, knockdown of H19 inhibited cell proliferation, migration and invasion, while overexpression of H19 reversed the inhibitory effect of Rg3 on the OC cells. In conclusion, ginsenoside Rg3 suppresses the proliferation, migration and invasion of OC cells by partially inhibiting the expression of lncRNA H19.
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http://dx.doi.org/10.18388/abp.2020_5343DOI Listing
May 2021

The employment of cynomolgus monkey as proprioceptive deficit model of the anterior cruciate ligament.

J Orthop Surg (Hong Kong) 2021 May-Aug;29(2):23094990211015519

Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.

Introduction: Clinically, a consensus of the treatment strategies of ACL grade 2 injury is not reached. Therefore, the present study established a proprioceptive deficit model of the ACL via an arthroscope to aid with further studying ACL grade 2 injury and treatment strategies.

Materials And Methods: 12 cynomolgus monkeys were randomly divided into the model group and the blank control group. In the model group, 1/4 of the ACL was cut under an arthroscope, whereas no intervention was performed in the blank control group. Physiological data including the maximum degree of knee flexion, the thigh circumstance and the calf circumference were measured, and the Pivot-shift, Anterior and Lachman tests were also performed. Moreover, electrophysiological data including somatosensory evoked potentials (SEPs) and motor nerve conduction velocity (MNCV) were measured. SEPs and MNCV were assessed for the latent period and amplitude.

Results: Comparing the data before and after the surgery, in the blank control group, no significant difference was observed. In the model group, significant difference was observed in the Pivot-shift, Anterior drawer and Lachman test ( < 0.05), indicating the instability of the ACL. Moreover, the latent period of SEPs and MNCV were significantly increased ( < 0.009), whereas the amplitude of SEPs and MNCV was significantly decreased ( < 0.009), indicating a degenerated proprioception of the knee joint.

Conclusions: Following cutting 1/4 of the ACL, the knee joint became unstable and proprioception was declined. The results indicated that the proprioceptive deficit model of the ACL was successfully established, which could promote further studying ACL injury.
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http://dx.doi.org/10.1177/23094990211015519DOI Listing
May 2021

Kynurenine metabolism and metabolic syndrome in patients with schizophrenia.

J Psychiatr Res 2021 Jul 8;139:54-61. Epub 2021 May 8.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, 100096, PR China. Electronic address:

Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD)/quinolinic acid (QUNA) in patients than in controls (all p < 0.01). Partial correlation analyses revealed that, in the patient group, QUNA and QUNA/KYN correlated positively with MS score (r = 0.24 and 0.27, respectively, both p < 0.025), and NAD/QUNA correlated negatively with MS score (r = -0.25, p = 0.002). Results of multiple regression analyses showed significant QUNA × group interactions in the model representing QUNA effects on MS score (β = 0.25) and a significant QUNA/KYN × group interaction in the model representing QUNA/KYN effects on MS score (β = 0.23) (both p < 0.001). Among all factors contributing to MS in schizophrenia, an interactive effect of schizophrenia itself and dysregulated KP plays a contributory role. Conceivably, modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.004DOI Listing
July 2021

Case Report: Complete Maternal Uniparental Isodisomy of Chromosome 5 (iUPD(5)mat) With Nonsense Variant in an Infant With Recurrent Diarrhea.

Front Genet 2021 6;12:668326. Epub 2021 May 6.

Center for Molecular Medicine, National Children's Medical Center, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.

Congenital diarrhea diseases are a heterogeneous group of conditions and are the major cause of neonatal mortality worldwide. Proprotein convertase 1/3 (PC1/3) deficiency has been associated with severe malabsorptive diarrhea, obesity, and certain endocrine abnormalities. We report an infant born to non-consanguineous parents who is diagnosed with PC1/3 deficiency due to nonsense homozygous variant (c.238 C>T, p.Arg80Ter) in the gene, identified by Trio-exome sequencing (Trio-ES). The baby girl presented with recurrent diarrhea, transient liver dysfunction and hypoglycemia. Trio-ES showed complete maternal uniparental isodisomy (iUPD) of chromosome 5. Our finding provides accurate genetic counseling to this family and expands the clinical spectrum of iUPD with pathogenic variants causing recessive disease.
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http://dx.doi.org/10.3389/fgene.2021.668326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134681PMC
May 2021

Overdosage of Gene Associated With Annular Pancreas Detected in Neonate Patients With 17q12 Duplication.

Front Genet 2021 7;12:615072. Epub 2021 May 7.

Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The annular pancreas (AP) is a congenital anomaly of the pancreas that can cause acute abdominal pain and vomiting after birth. However, the genetic cause of AP is still unknown, and no study has reported AP in patients with 17q12 duplication. This study retrospectively analyzed the next-generation sequencing (NGS) data of individuals from January 2016 to June 2020 for 17q12 duplication. To identify the function of the key gene of in the 17q12 duplication region, human mRNA was microinjected into LiPan zebrafish transgenic embryos. A total of 19 cases of 17q12 duplication were confirmed. AP was diagnosed during exploratory laparotomy in four patients (21.1%). The other common features of 17q12 duplication included intellectual disability (50%), gross motor delay (50%), and seizures/epilepsy (31.58%). The ratio of the abnormal pancreas in zebrafish was significantly higher in the overexpression models. In conclusion, we first reported AP in patients with duplication of the 17q12 region, resulting in the phenotype of 17q12 duplication syndrome. Furthermore, our zebrafish studies verified the role of the gene in pancreatic development.
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http://dx.doi.org/10.3389/fgene.2021.615072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138176PMC
May 2021

Adiponectin Mediates the Protection of HS Against Chronic Restraint Stress-Induced Cognitive Impairment Attenuating Hippocampal Damage.

Front Behav Neurosci 2021 5;15:623644. Epub 2021 May 5.

Department of Neurology, The Affiliated Nanhua Hospital, University of South China, Hengyang, China.

Emerging evidence shows that chronic restraint stress (CRS) can induce cognitive dysfunction, which involves in hippocampal damage. Our recent research reveals that hydrogen sulfide (HS), a novel gasotransmitter, protects against CRS-induced cognitive impairment, but the underlying mechanism remains unclear. Adiponectin, the most abundant plasma adipokine, has been shown to elicit neuroprotective property and attenuate cognitive impairment. Hence, the present work was aimed to explore whether adiponectin mediates the protective effect of HS on CRS-induced cognitive impairment by inhibiting hippocampal damage. Results found that administration of Anti-Acrp30, a neutralizing antibody of adiponectin, obviously reverses sodium hydrosulfide (NaHS, an exogenous HS donor)-induced the inhibition on CRS-induced cognitive impairment according to Y-maze test, Novel object recognition (NOR) test, and Morris water maze (MWM) test. In addition, Anti-Acrp30 blocked the protective effect of NaHS on hippocampal apoptosis in rats-subjected with CRS as evidenced by the pathological changes in hippocampus tissues in hematoxylin and eosin (HE) staining and the increases in the amount of the condensed and stained to yellowish-brown or brownish yellow neuron nucleuses in terminal deoxynucleotidyl transferase transfer-mediated dUTP nick end-labeling (TUNEL) staining as well as the expression of hippocampal pro-apoptotic protein (Bax), and a decrease in the expression of hippocampal anti-apoptotic protein (Bcl-2). Furthermore, Anti-Acrp30 mitigated the inhibitory effect of NaHS on CRS-induced oxidative stress as illustrated by the up-regulation of malondialdehyde (MDA) content and the down-regulation of superoxide dismutase (SOD) activity and glutathione (GSH) level in the hippocampus. Moreover, Anti-Acrp30 eliminated NaHS-induced the reduction of endoplasmic reticulum (ER) stress-related proteins including binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), and Cleaved Caspase-12 expressions in the hippocampus of rats-exposed to CRS. Taken together, these results indicated that adiponectin mediates the protection of HS against CRS-induced cognitive impairment through ameliorating hippocampal damage.
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http://dx.doi.org/10.3389/fnbeh.2021.623644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131522PMC
May 2021