The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Nitrogen transport and sources in urban stormwater with different rainfall characteristics.

Nitrogen pollution in urban stormwater has led to serious quality issues in urban water. Nitrogen pollution mitigation requires fully understanding the transport process and major nitrogen sources in urban stormwater. In this study, the concentrations and flux of various nitrogen forms during urban stormwater transport were analyzed. It was found that the concentration and flux of NO3--N and NH3-N decreased in the order of roof runoff, road runoff, and drainage runoff, while the concentration and flux of dissolved organic nitrogen (DON) and particulate nitrogen (PN) were found to be the highest in road runoff. Source quantification found that roof runoff (34%) and rainwater (34%) were the main contributors to nitrate pollution during light and moderate rains (<25 mm), while road runoff was identified as the major source (49%) of nitrate pollution during heavy rains (>25 mm) due to the large road runoff volume. Regarding particulate organic nitrogen (PON), the road runoff in commercial areas contributed most (23%) to PON pollution during light and moderate rains, while the runoff generated from pervious surfaces and drainage sediments were the primary two sources (22%) of PON during heavy rains. Moreover, the influence of rainfall characteristics on nitrate and PON source contributions was identified. The results show that antecedent dry periods were an important factor influencing nitrogen source contributions during light and moderate rains, while rainfall amount and intensity were critical factors impacting the nitrogen source contributions during heavy rains. Taking various transport processes, source contributions, and rainfall characteristics into consideration, several recommendations were given for the mitigation of nitrogen pollution in urban stormwater. This study can provide a useful perspective to understand the transport and sources of nitrogen, thus developing constructive strategies to control urban nonpoint source pollution management.

The roles of inactivated vaccines in older patients with infection of Delta variant in Nanjing, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.

Case Report: Primary Indolent Epstein-Barr Virus-Positive T-Cell Lymphoproliferative Disease Involving the Central Nervous System.

Background: T-cell lymphoproliferative disease (T-LPD), characterized by primary Epstein-Barr virus (EBV) infection and clonal proliferation of T cells, occurs both in systemic and non-lymphatic organs. However, isolated indolent EBV-positive T-LPD involving the central nervous system has not been reported. Case Presentation: A 48-year-old male who complained of headache, blurred vision, and weakness of the left lower limb for 1 month was hospitalized in our department. Neither neurological deficit nor palpable lymphadenopathy had been found. Bone marrow and laboratory tests had shown no abnormality as well. Enhanced MRI demonstrated enhanced cotton-like lesions up to 20 mm in diameter located in the right frontal, temporal, parietal and left parietal, occipital lobes with perifocal edema. Neuronavigation-assisted mini-craniotomy was performed to achieve total excision of the right temporal superficial lesion and identify the diagnosis. Pathological and EBV analysis described the lesion as indolent EBV-positive T-cell lymphoproliferative disease of the central nervous system (CNS). Then, a therapeutic regimen including whole-brain irradiation, chemotherapy, prednisolone, and aciclovir was given. Serial radiological imaging showed no signal of recurrence at 5 months' follow-up. Conclusion: Primary indolent T-LPD in the central nervous system is quite rare, and it needs to be distinguished from aggressive cerebral T-cell lymphoma, metastatic tumors, and other CNS lesions.

C-MYC induces idiopathic pulmonary fibrosis via modulation of miR-9-5p-mediated TBPL1.

We sought to pinpoint the potential role of C-MYC in pulmonary fibroblast proliferation in idiopathic pulmonary fibrosis (IPF) and its mechanism. A mouse model of IPF was established by injection of bleomycin. C-MYC and miR-9-5p expression was determined by RT-qPCR and Western blot analysis. The interaction among C-MYC, miR-9-5p, and TBPL1 was detected by ChIP assay and dual luciferase reporter gene assay. After alteration of C-MYC, miR-9-5p, and TBPL1, their roles in pulmonary fibrosis and collagen fiber deposition in mice as well as proliferation and differentiation of pulmonary fibroblasts were assessed. Upregulated C-MYC expression was seen in the lung tissues of IPF mice and its silencing retarded IPF in mice. C-MYC could activate miR-9-5p that negatively regulated TBPL1 expression. Up-regulated C-MYC promoted proliferation and differentiation of pulmonary fibroblasts by inhibiting TBPL1 via activation of miR-9-5p, thus triggering IPF. Moreover, in the lung tissues-derived cells of IPF mice, C-MYC inhibitor, 10,058-F4, was observed to inhibit miR-9-5p expression, thereby repressing pulmonary fibrosis by up-regulating TBPL1. Our data provided evidence pinpointed the aggravative role of C-MYC in IPF by activating miR-9-5p to regulate TBPL1 expression.

Gospel of malignant Glioma: Oncolytic virus therapy.

Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients. Currently, gliomas are mainly treated with surgery, postoperative radiotherapy, and chemotherapy. However, the curative effects of these treatments are not satisfactory. Oncolytic virus (OV) is a novel treatment which works by activating the immune functions and inducing apoptosis of tumor cells. The OV propagates indefinitely in the host cell, eventually leading to the death of host cell. Subsequently, a large number of antigens and signal molecules are released which exert antitumor immunity. Several preclinical and clinical studies have shown that G207, DNX2401, Zika and other viruses have important roles in malignant tumors. For example, these viruses can reduce the growth of tumor cells without causing severe complications. However, the known OVs have not been clearly classified. Herein, we divided OVs into neurotropic and non-neurophilic OVs based on whether the OVs are naturally neurotropic or not. The therapeutic effects of each group were compared. Finally, challenges encountered in the clinical application of OVs in the treatment of malignant gliomas were summarized.

Long-term survival in an acute promyelocytic leukemia patient with recurrent granulocytic sarcomas: A case report.

RATIONALE: Granulocytic sarcoma (GS) is an extramedullary myeloid tumor composed of immature cells of the granulocytic series. It rarely occurs in acute promyelocytic leukemia (APL). No case of long-term survival in an APL patient with recurrent GS has been reported. PATIENT CONCERNS: A 54-year-old female patient was diagnosed with APL in 1995 and has been in complete remission (CR) of bone marrow morphology for 24 years; however, recurrent GS occurred successively in ovary, breast, spine, body of sternum, lymph nodes, soft tissues from 2004 to 2019. DIAGNOSES: The immunohistochemistry confirmed the diagnosis of GS, and fluorescence in situ hybridization (FISH) revealed its origin from APL. INTERVENTIONS: She received surgery, and had an excellent response to all-trans retinoic acid (ATRA), DA (daunorubicin combined with cytarabine) regimens, and arsenic trioxide (ATO). OUTCOMES: The patient achieved CR in March 2020 after radiotherapy followed by ATO and ATRA. So far, she is still in follow-up. LESSONS: It is rare that recurrent GS at multiple sites is involved in APL patient with bone marrow morphology in CR. It is interesting to observe a long-term excellent response to ATRA, chemotherapy and ATO. Although multiple recurrence of GS in patients with APL is rare, the data in this case highlight the need for individualized treatment when such conditions occur.

Scenario for the use of effusion-peritoneal shunt necessary against subdural effusion secondary to decompressive craniectomy.

OBJECTIVES: This study aimed to summarize the surgical strategies for subdural effusion secondary to decompressive craniectomy (SESDC) and discuss the applicable scenarios of effusion-peritoneal shunt (EP shunt). METHODS: A total of 53 consecutive patients with SESDC were screened out of 7569 cases. The SESDC was divided into five types, and the treatment methods of each type were analyzed and compared. According to the implementation strategy of cranioplasty (CP), patients were divided into CP-first and delayed-CP groups. The differences in surgical methods were compared between the two groups. RESULTS: All patients with SESDC in this cohort had undergone cranioplasty. Subcutaneous puncture and aspiration (SPAA) proved ineffective. Only 2/30 patients in the CP-first group used EP shunt, while 6/19 patients in the delayed-CP group used EP shunt; the difference was statistically significant (P = 0.03). A significant difference was found in the use of EP shunt among type 1, type 2, and type 5 SESDC (χ2 = 6.778, P = 0.034). CONCLUSIONS: CP combined with other treatments could cure most SESDC. EP shunt should be used preferentially in some specific scenarios in which CP cannot be performed first, rather than as a backup measure that can only be used when other preceding treatments fail.

Identification of the regulatory networks and hub genes controlling alfalfa floral pigmentation variation using RNA-sequencing analysis.

BACKGROUND: To understand the gene expression networks controlling flower color formation in alfalfa, flowers anthocyanins were identified using two materials with contrasting flower colors, namely Defu and Zhongtian No. 3, and transcriptome analyses of PacBio full-length sequencing combined with RNA sequencing were performed, across four flower developmental stages. RESULTS: Malvidin and petunidin glycoside derivatives were the major anthocyanins in the flowers of Defu, which were lacking in the flowers of Zhongtian No. 3. The two transcriptomic datasets provided a comprehensive and systems-level view on the dynamic gene expression networks underpinning alfalfa flower color formation. By weighted gene coexpression network analyses, we identified candidate genes and hub genes from the modules closely related to floral developmental stages. PAL, 4CL, CHS, CHR, F3'H, DFR, and UFGT were enriched in the important modules. Additionally, PAL6, PAL9, 4CL18, CHS2, 4 and 8 were identified as hub genes. Thus, a hypothesis explaining the lack of purple color in the flower of Zhongtian No. 3 was proposed. CONCLUSIONS: These analyses identified a large number of potential key regulators controlling flower color pigmentation, thereby providing new insights into the molecular networks underlying alfalfa flower development.

Characterization of the complete chloroplast genome of Delphinium grandiflorum L.

Delphinium grandiflorum L. is a perennial herb, and has very high medicinal value. However, the evolutionary relationship analysis of D. grandiflorum is limited. Its cp genome was 157,339 bp in length, containing a pair of inverted repeated regions (52,304 bp), separated by a large single copy region of 88,098 bp, and a small single copy region of 16,937 bp. Moreover, a total of 117 functional genes were annotated, including 79 mRNA, 30 tRNA genes, and 8 rRNA genes. The phylogenetic relationships inferred that D. grandiflorum was closely related to Gymnaconitum gymnandrum. This study will provide a theoretical basis for species identification and biological research.

Transcriptomic analysis of Lycium ruthenicum Murr. during fruit ripening provides insight into structural and regulatory genes in the anthocyanin biosynthetic pathway.

Fruit development in Lycium ruthenicum Murr. involves a succession of physiological and biochemical changes reflecting the transcriptional modulation of thousands of genes. Although recent studies have investigated the dynamic transcriptomic responses during fruit ripening in L. ruthenicum, most have been limited in scope, and thus systematic data representing the structural genes and transcription factors involved in anthocyanin biosynthesis are lacking. In this study, the transcriptomes of three ripening stages associated with anthocyanin accumulation, including S1 (green ripeness stage), S2 (skin color change) and S3 (complete ripeness stage) in L. ruthenicum were investigated using Illumina sequencing. Of a total of 43,573 assembled unigenes, 12,734 were differentially expressed during fruit ripening in L. ruthenicum. Twenty-five significantly differentially expressed structural genes (including PAL, C4H, 4CL, CHS, CHI, F3H, F3'H, F3'5'H, DFR, ANS and UFGT) were identified that might be associated with anthocyanin biosynthesis. Additionally, several transcription factors, including MYB, bHLH, WD40, NAC, WRKY, bZIP and MADS, were correlated with the structural genes, implying their important interaction with anthocyanin biosynthesis-related genes. Our findings provide insight into anthocyanin biosynthesis and regulation patterns in L. ruthenicum and offer a systematic basis for elucidating the molecular mechanisms governing anthocyanin biosynthesis in L. ruthenicum.

CA-125-indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery.

BACKGROUND: There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS). METHODS: We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration. RESULTS: The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p < 0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31 days (ranging from 1 to 391 days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of < 1.68 × nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p = 0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level ≤ 1.68 × nadir at relapse (69.4 and 13.8 months) were longer than those with a CA-125 level > 1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p = 0.02 and 0.04 respectively). CONCLUSIONS: The increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.

G-quadruplex-hemin DNAzyme-amplified colorimetric detection of Ag+ ion.

A G-quadruplex-hemin DNAzyme-amplified Ag(+)-sensing method was developed based on the ability of Ag(+) to stabilize C-C mismatches by forming C-Ag(+)-C base pairs. In this method, only one unlabelled oligonucleotide strand was used. In the absence of Ag(+), the oligonucleotide strand formed an intramolecular duplex. The G-rich sequence in the oligonucleotide was partially caged in this duplex structure and cannot fold into the G-quadruplex structure. The addition of Ag(+) promoted the formation of another intramolecular duplex in which C-C mismatches were stabilized by C-Ag(+)-C base pairs, leading to the release of the G-rich sequence which can fold into a G-quadruplex capable to bind hemin to form a catalytically active G-quadruplex-hemin DNAzyme. As a result, a UV-vis absorbance increasing was observed in the H(2)O(2)-ABTS (2,2'-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid) reaction system. This "turn-on" process allowed the detection of aqueous Ag(+) at concentrations as low as 6.3 nM using a simple colorimetric technique, showing a high selectivity over a range of other metal ions.

Ag+ and cysteine quantitation based on G-quadruplex-hemin DNAzymes disruption by Ag+.

Some G-quadruplex-hemin complexes are DNAzyme peroxidases that efficiently catalyze H(2)O(2)-mediated reactions, such as the oxidation of ABTS (2,2'-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid) by H(2)O(2). Since Ag(+) chelates guanine bases at the binding sites are involved in G-quadruplex formation, the presence of Ag(+) may disrupt these structures and inhibit the peroxidase activity of G-quadruplex-hemin DNAzymes. On the basis of this principle, a highly sensitive and selective Ag(+)-detection method was developed. The method allows simple detection of aqueous Ag(+) with a detection limit of 64 nM and a linear range of 50-3000 nM. Cysteine (Cys) is a strong Ag(+)-binder and competes with quadruplex-forming G-rich oligonucleotides for Ag(+)-binding, promoting the reformation of G-quadruplexes and increasing their peroxidase activity. Therefore, the Ag(+)-sensing system was also developed as a Cys-sensing system. This "turn-on" process allowed the detection of Cys at concentrations as low as 50 nM using a simple colorimetric technique. The Cys-sensing system could also be used for the detection of reduced glutathione (GSH). Neither the Ag(+)-sensing nor the Cys-sensing systems required labeled oligonucleotides. In addition, both gave large changes in absorbance signal that could be observed by the naked eye. Thus, a simple visual method for Ag(+)- or Cys-detection was developed.

[Clinical and laboratory study of 4 cases of myelodysplastic syndromes with t (1;3) (p36; q21)].

OBJECTIVE: To study the clinical features of myelodysplastic syndromes (MDS) patients with t (1; 3) (p36; q21) and the expression of the involved genes. METHODS: 4 cases of MDS with t (1; 3) (p36; q21) were reported. The expression level of two transcription forms (PR-containing form MEL1 and PR-lacking form MEL1s) of MEL1 gene in normal fetus tissues, 2 healthy donor bone marrows and bone marrows from 3 MDS patients with t (1; 3) (p36; q21) were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: MDS patients with t (1; 3) (p36; q21) mainly presented with debility. Hemogram was macrocytic anemia, normal or elevated white blood cell and platelet counts. The bone marrow showed tri-lineage dysplasia especially dysmegakaryocytopoiesis. The patients had poor prognosis. MEL1 form was mainly expressed in the normal fetus tissues and healthy bone marrows, while the bone marrow cells from MDS patients with t (1; 3) (p36; q21) mainly or only expressed MEL1s. CONCLUSIONS: MDS patients with t (1; 3) (p36; q21) may be a new unique entity. Overexpression of MEL1s induced by t (1; 3) (p36; q21) might play an important role in the pathogenesis of this entity.