Objective To investigate the expressions of 12 cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-α,IFN-γ,TNF-α)and procalcitonin in patients with infective endocarditis(IE).Methods Ten IE patients admitted to our hospital from December 2021 to December 2022 were included into the IE group,10 patients with non-infectious and non-rheumatic valvular diseases who were admitted to our hospital at the same period were randomly selected as the control group,and blood sampling of all patients were conducted at admission.The expressions of 12 cytokines and blood routine indexes were detected by flow cytometry,and the level of procalcitonin was detected by ELISA.The correlations among the expression levels of cytokines in IE patients were analyzed by Pearson method and the correlations of IL-8 level and white blood cell count with procalcitonin in IE patients were analyzed by Spearman method.Results Compared with the control group,the levels of cytokines of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ and IL-12p70 in the IE group were significantly increased(P<0.05),the white blood cell count,neutrophil percentage and procalcitonin were significantly increased(P<0.05).There was no significant difference in the percentage of monocytes between the two groups(P>0.05).IFN-α of IE patients was positively correlated with IL-2,TNF-α,IL-1β and IL-12p70,IL-2 was positively correlated with TNF-α and IL-1β,IL-12p70 was positively correlated with IFN-γ,and procalcitonin was significantly positively correlated with IL-8 and white blood cell count,with statistically significant differences(P<0.05).Conclusion The levels of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ,IL-12p70 and procalcitonin in IE patients are significantly higher than those in the normal population,and the detections of these indicators are of guiding significance for the early diagnosis of IE and the evaluation of the severity of the disease.

ObjectiveIn kinesin-3, the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A. The function of this neck hinge for controlling processive movement, however, remains unclear. MethodsWe made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay. ResultsIn KIF13B, the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity, while the removal of this proline increases the both. In KIF1A, the deletion of entire flexible neck hinge merely enhances the processivity. The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1. ConclusionThe neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility, which provides a novel strategy to reshape the processive movement of kinesin motors.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the effect of canagliflozin combined with enalapril on diabetic nephropathy(DN).Methods DN patients were randomly divided into control group and treatment group.All patients in 2 groups received basic treatment of recombinant human insulin injection,and the control group was orally administered enalapril tablet 10 mg(qd).The treatment group was given orally canagliflozin tablet 100 mg(qd)on the basis of the control group.Both groups were treated for 8 weeks.Renal function,blood glucose index,serum vascular endothelial growth factor(VEGF),transforming growth factor-β(TGF-β),homocysteine(HCY)levels,clinical efficacy and incidence of adverse drug reactions were compared between 2 groups.Results There were 71 cases were included in the control group and 73 cases in the treatment group.After treatment,β2 microglobulin(β2-MG)in treatment group and control group were(0.21±0.03)and(0.28±0.04)mg·L-1;blood urea nitrogen(BUN)were(4.23±0.42)and(5.58±0.65)mmol·L-1;serum creatinine(SCr)were(89.32±8.29)and(101.25±10.18)pmol·L-1;24 h microalbumin(mAlb)were(49.38±5.06)and(58.21±6.43)mg;glycosylated hemoglobin(HbA1c)were(6.10±0.11)％and(6.45±0.16)％;2 h postprandial blood glucose levels were(6.05±0.78)and(7.68±1.82)mmol·L-1;fasting blood glucose(FBG)were(5.02±0.32)and(5.67±0.65)mmol·L-1;VEGF levels were(350.18±20.04)and(389.04±24.16)pg·mL-1;TGF-β were(148.32±16.57)and(168.24±20.02)pg·mL-1;HCY were(13.12±2.38)and(19.35±3.21)pmol·L-1,the differences were statistically significant(all P＜0.05).After treatment,the total effective rate of treatment group and control group were 83.56％(61 cases/73 cases)and 67.61％(48 cases/71 cases),the difference was statistically significant(P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.85％and 4.23％,with no significant difference(P＞0.05).Conclusion Canagliflozin combined with enalapril is effective in the treatment of diabetic nephropathy,which can improve renal function,regulate blood glucose metabolism,and down-regulate serum VEGF,TGF-β and HCY levels,and is safe and reliable.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Humans ; Granuloma, Pyogenic/pathology* ; Hemangioma, Capillary

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; Incidence

OBJECTIVE: To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research. METHODS: The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified. RESULTS: Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target. CONCLUSION YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.
Humans ; Network Pharmacology ; Quercetin ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Esophageal Neoplasms ; Drugs, Chinese Herbal

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.