Objective:To investigate whether the lung specific X protein(LUNX)gene can serve as a prognostic biomarker for non-small cell lung cancer related to immune cell infiltration.Methods:A total of 280 non-small cell lung cancer patients admitted to Hengshui People's Hospital from January 2020 to January 2023 were selected to detect the expression of LUNX gene in cancer tissue and adjacent tissues,and to analyze the relationship between LUNX gene and immune cell infiltration and prognosis survival status in the tumor microenvironment.Results:Compared with adjacent tissues,the expression level and positive rate of LUNX gene in non-small cell lung cancer tissue were increased,which were related to differentiation degree,lymph node metastasis and tumor staging(P<0.05).GEPIA database analysis showed that the LUNX gene was only slightly expressed or not expressed in other tissues,while its expression was elevated in LUAD and LUSC(P<0.05).The copy number of LUNX gene and LUNX gene were related to the level of immune cell infiltration(P<0.05).Survival analysis showed that high expression of the LUNX gene was associated with patient survival prognosis(P<0.05).Conclusion:The LUNX gene is specifically expressed in non-small cell lung cancer tissue,affecting the level of immune cell infiltration in non-small cell lung cancer,leading to an imbalance in the immune microenvironment,and is an important mechanism for causing patients prognostic death,which can be used as a prognostic biomarker for evaluating immune cell infiltration.

Atopic dermatitis (AD) is a common chronic inflammatory disease that often coexists with atopic diseases such as asthma, allergic rhinitis, and food allergies. In recent years, more and more studies have shown that AD is associated with various diseases such as cardiovascular diseases, autoimmune diseases, and mental disorders, which exacerbate the disease burden on patients with AD and severely affect their quality of life. This review summarizes AD-associated comorbidities reported in previous literature, analyzes their possible common pathogenesis, and explores potential treatments.

Objective To explore the effects of four extralevator abdominoperineal excision(ELAPE)procedures on the biomechanics of female pelvic floor through finite element analysis.Methods Six finite element models of the female pelvic floor were established,including a normal model,an ELAPE model,and four individual models.The maximum stress in each model was measured under the same pressure,and the stress distribution was observed.Results The maximum stress of non-levator ani muscle tissues on the partially reserved side and totally removed side of the levator ani muscle were 3.101±0.133 and 4.868±0.123 MPa in individual model 1,respectively,which were lower than the maximum stress in the ELAPE model(5.111±0.081 MPa;both P<0.01).The maximum stress in the non-levator ani muscle tissue were 5.138±0.091 MPa on both sides in individual model 2,which were not significantly different from that in the ELAPE model(P>0.05).The maximum stress of non-levator ani muscle tissues were 4.700±0.105 and 3.653±0.156 MPa in individual models 3 and 4,respectively,which were lower than the maximum stress in the ELAPE model(both P<0.01).Conclusion Three ELAPE procedures,including ELAPE with unilateral levator ani muscle resection plane close to the rectum,and the bilateral pubococcygeal muscle lateral resection of levator ani muscle and levator ani muscle in front of the rectum preserved could decrease stress in the non-levator ani muscle tissue on both sides.The effect is evident on the levator ani muscle partially reserved side of ELAPE with unilateral levator ani muscle resection plane close to the rectum.ELAPE with unilateral levator ani muscle resection plane close to the pelvic wall has no significant reduction effect on the non-levator ani muscle tissue on either side.ELAPE模型(均P<0.01).

Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.

Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.

Objective:To analyze and compare the practical value of serum cystatin C(Scys C)and serum creatinine(SCr)in the assessment of kidney function in older adults.Methods:A retrospective, cross-sectional study was performed in 2 450 participants who were divided into a non-elderly group(<65 years)and an elderly group(≥65 years).Glomerular filtration rate(GFR), Scys C and SCr were measured by 99mTc-DTPA clearance, particle-enhanced immunoturbidimetry and an oxidase method, respectively.The χ2 test was used to compare increases in percentage of Scys C and SCr at the same GFR level.The screening value of Scys C and SCr for GFR<60 ml·min -1·1.73m -2was evaluated by the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Values of 95% reference ranges were established for Scys C and SCr at different GFR levels. Results:The proportions of the general population with increased Scys C were 82.74%(556/672)and 94.74%(90/95), respectively, for GFR levels between 30~59 ml·min -1·1.73m -2and <30 ml·min -1·1.73m -2, while only 38.24%(257/672)and 75.79%(72/95)had elevated SCr levels( χ2=278.328, 13.571, both P<0.001).For the above GFR intervals, the proportions of older adults with increased Scys C were 84.81%(240/283)and 100.00%(43/43)respectively, and the proportions for non-elderly adults with increased Scys C were 81.23%(316/389)and 90.38%(47/52)( χ2=1.463, 4.364, P=0.226, 0.037), respectively.The screening value of Scys C for GFR<60 ml·min -1·1.73m -2was slightly better than SCr in terms of sensitivity, specificity and the Youden index.However, the sensitivity and specificity of Scys C in older adults were 76.4% and 75.7%, respectively, both lower than 78.7% and 84.0% in non-older adults.The variability of Scys C increased progressively with age.The reference range for Scys C was higher in older adults than in non-older adults at the same GFR level. Conclusions:When screening for GFR<60 ml·min -1·1.73m -2, the sensitivity and specificity of Scys C are slightly better than those of SCr, but are lower in older adults than in non-older adults.Scys C levels are higher and more variable in older adults.Using Scys C to assess GFR may lead to over-diagnosis of chronic kidney disease in older adults.

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Logistic Models ; Phenotype ; Risk Factors

Objective To evaluate the effectiveness of computer aided design (CAD) and three bit printing in the management of orthognathic surgery.Methods A total of 5 cases of patients with jaw deformity were involved in this study;jaw teeth and CT scanning laser scanning hefore surgery,virtual surgery design of 3D reconstruction and fusion data were analyzed,according to the design scheme of double jaw surgery combined with genioplasty;design and 3D printing of maxillary Le Fort Ⅰ osteotomy,genioplasty titanium alloy resin osteotomy and positioning guide,sagittal split ramus osteotomy by 3D printing and plate technology were used in this approach.The postoperative results were compared with the surgical planning by three-dimensional measurement and statistical analysis.Results When the operation guide plate was applied smoothly,the maximum error for maxilla was 1.2 mm (0.3-1.2 mm),and the maximum error for genioplasty was 1.7 mm,(0.5-1.7 mm),and the mean error was less than 1 mm.Follow-up for 12 months showed no adverse reaction.Conclusions Three dimensional printing surgical guide plate can accurately provide the osteotomy information,effectively control the jaw movement,and improve the orthognathic surgery accuracy of patients with partial jaw deformity.

Telemedicine can optimize deployment of medical resources and minimize diagnosis discrepancies.Formulation of a rational project pricing and scientific compensation policy will be conducive to its future development. The concept of human resource consumption in RBRVS was used as reference to improve the activity-based costing ( ABC ) method. The authors sorted out the resource cost repository, identified the activity system, classified the motivation resources into respective activity cost repositories, and calculated the cost of respective cost object distribution.The cost of three telemedicine service items(remote single discipline consultation, remote image consultation and remote pathology consultation were 119.69, 147.03 and 161.61 yuan respectively) was calculated by the improved ABC.It can better indicate project costs than that calculated by the traditional ABC(137.30, 147.17 and 144.08 yuan), and proves more consistent with the existing prices of other province(134.00, 150.00 and 174.00 yuan).