LINC01094 promotes human nasal epithelial cell epithelial-to-mesenchymal transition and pyroptosis via upregulating HMGB1.

BACKGROUND: Excessive epithelial-to-mesenchymal transition (EMT) of nasal epithelial cells (NECs) play a prominent role in chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis. Long intergenic non-coding RNA 01094 (LINC01094) was previously reported to be overexpressed in CRSwNP, while the regulatory mechanism by which LINC01094 regulates CRSwNP progression remains unclear. Our study aimed to investigate the role of LINC01094 in CRSwNP development. METHODS: hNEC were isolated from tissues of controls and CRSwNP patients and stimulated with interleukin (IL)-13. 3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay was employed to analyze hNEC viability. Flow cytometry was employed to analyze pyroptosis. Immunofluorescence was employed to analyze Snail nuclear translocation. The interactions between LINC01094, fused in sarcoma (FUS) and high mobility group box-1 (HMGB1) were analyzed by RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: LINC01094 and EMT-related proteins were markedly upregulated in nasal polyp tissues of CRSwNP. LINC01094 knockdown inhibited IL-13-induced hNEC EMT and pyroptosis. LINC01094 promoted HMGB1 expression in CRSwNP by binding with FUS. HMGB1 promoted Snail nuclear import in GSK-B phosphorylation-dependent manner. CONCLUSION: LINC01094 facilitated hNEC EMT and pyroptosis in CRSwNP by activating the HMGB1/GSK-B Snail axis, which suggested that LINC01094 might serve as a biomarker and therapeutic target in CRSwNP.

[Research progress on uranium induced human renal injury and its risk prediction].

Uranium has both radiotoxicity and chemical toxicity. Low enriched uranium is mainly chemically toxic, the kidney is the target organ of uranium chemical toxicity. However, due to the differences among species and the mixed effects of chemical toxicity and radiotoxicity, the dose effect relationship of uranium is not clear, and the current standards in China do not provide chemical toxicity limits for uranium workplaces. This paper reviews the data of acute and chronic human uranium exposure, dose effect relationship and renal injury risk prediction literature at home and abroad, providing reference for the health protection of uranium workers and the establishment of chemical limits in uranium workplaces.

[Research advances on invasive fungal infections after burns].

Invasive fungal infection (IFI) is one of the serious complications in burn patients. The gradual development and application of broad-spectrum antibiotics in recent years has led to a serious dysbiosis of the flora, while the widespread prophylactic use of antifungal drugs has led to an increasing number of drug-resistant fungi. The clinical treatment of IFI is difficult and the prognosis is poor. The mortality of burn patients caused by IFI is increasing year by year. This paper reviews the epidemiologic characteristics, related risk factors, diagnostic methods, and treatment progress of IFI after burns, aiming to provide new ideas and reference for the prevention and treatment of IFI after burns.

[Design for online monitoring of occupational hazard factors based on internet of things].

At present, there are disadvantages with the detection for occupational hazard factors, such as insufficient monitoring data, poor timeliness, weak representativeness, long detection cycles, and inability to continuously monitor. Taking advantages of internet of things technology, an online monitoring platform for occupational hazard factors has been designed. The platform collects the concentration (intensity) of hazard factors through sensors, transmits the occupational hazards data collected online in realtime. The online monitoring cloud center for occupational hazard factors processes and analyzes online monitoring data in realtime, stores the hazard factors data to form database management, and provides user application services to form an intelligent online monitoring service model for occupational hazard factors. Based on the online monitoring platform of occupational hazard factors, multi-level government health supervision departments and employers can grasp the status of hazard factors in real time, which is conducive to improving the level of occupational hazard supervision.

[Regulation of colony-stimulating factor 1 receptor inhibitor pexidartinib on the senescence of mouse bone marrow-derived macrophages stimulated by lipopolysaccharide].

Objective: To investigate the effects of colony-stimulating factor 1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) on the senescence of bone marrow-derived macrophages (BMDM) stimulated by lipopolysaccharide (LPS). Methods: BMDM were isolated and cultured from femurs and tibiae of 10 male C57BL/6 mice aged 6-8 weeks (obtained from Laboratory Animal Center of Guizhou Medical University). They were divided into blank control group, LPS group (treated with 1 µg/ml LPS for 24 h) as well as low, medium and high concentration PLX3397 pretreatment groups (treated with 100, 500 and 1 000 nmol/L PLX3397 for 4 h respectively followed by 1 µg/ml LPS for 24 h). The corresponding markers of macrophages were detected by flow cytometry. Cell viability was detected by cell counting kit-8 and cellular senescence was detected by senescence-associated-ß-galactosidase (SA-ß-gal) staining. Meanwhile, protein expressions of cycle-dependent kinase inhibitor p16, p21 and CSF-1R were detected by Western blotting, and the expressions of p16 and p21 were detected by intracellular immunofluorescence. Real-time fluorescence quantitative PCR (RT-qPCR) was used to investigate the mRNA levels of senescence-associated secretory phenotype (SASP) genes including interleukin (IL), IL-1ß, chemokine-1/10 (CXCL-1/10), matrix metalloproteinase-8 (MMP-8), and transforming growth factor-ß (TGF-ß). Results: The rate of SA-ß-gal positive staining in medium and high concentration PLX3397 pretreatment groups [(39.33±4.93)% and (36.33±3.06)% respectively] were significantly downregulated compared with LPS group [(52.00±3.00)%] (P=0.020, P=0.005). The expression of CSF-1R protein in low, medium and high concentration PLX3397 pretreatment groups were (0.74±0.18, 0.61±0.07, 0.54±0.06), all of which were significantly lower than that in LPS group (1.16±0.08) (P=0.013, P=0.002, P<0.001). The expression levels of CSF-1R mRNA in low, medium and high concentration PLX3397 pretreatment groups (1.04±0.06, 0.90±0.05, 1.18±0.08) showed similar trend (2.90±0.25) (P<0.001). The average fluorescence intensity of p16 in all PLX3397 pretreatment groups were 49.76±3.65, 48.21±1.72, 47.99±1.26 respectively, which were significantly lower than that in LPS group (66.88±5.85) (P=0.001, P<0.001, P<0.001). The average fluorescence intensity of p21 in medium and high concentration PLX3397 pretreatment groups were (34.43±3.62, 30.13±0.86), significantly lower than that in LPS group (46.82±5.33) (P=0.043, P=0.007). The expression of p16 protein in low, medium and high concentration PLX3397 pretreatment groups (0.56±0.04, 0.55±0.04, 0.35±0.19) were significantly lower than that in LPS group (0.98±0.10) (P=0.003, P=0.002, P<0.001), as well the expression of p21 protein (0.69±0.20, 0.42±0.08, 0.26±0.14) (P=0.032, P=0.002, P<0.001). According to the results of RT-qPCR, the expressions of IL-6, IL-1ß, CXCL-1, CXCL-10 and MMP-8 in PLX3397 pretreatment groups were significantly lower than those in LPS group (P<0.001), while the expression of TGF-ß increased (P<0.001). Conclusions: LPS could induce the cell senescence, increase the secretion of SASP and aggravate local inflammation by activating the CSF-1R on the cell surface of bone marrow-derived macrophages. CSF-1R inhibitor PLX3397 might attenuate CSF-1R activation associated with LPS and inhibit the senescence of bone marrow-derived macrophages induced by LPS.

[Analysis of noise reduction measures in a noise workshop handover control room].

Objective: To explore the sound insulation, sound absorption and other noise reduction transformation methods in a noise workshop handover control room. Methods: In December 2021, through the occupational health investigation and on-site testing of the handover control room of a noise workshop, the causes of excessive noise were analyzed, and the transformation design scheme to reduce noise was proposed and the effect was analyzed. Results: Before the transformation, the peak frequency band noise intensity of the noise workshop handover control room was 112.8 dB (A), and the peak frequency was 1000 Hz. After noise reduction, the theoretical calculated control value was 61.0 dB (A), and the measured noise intensity was 59.8 dB (A) . Conclusion: The noise intensity of the handover control room is reduced after noise reduction, which is in line with the contact limit requirements of the control room in GBZ 1-2010 "Hygienic Standards for the Design of Industrial Enterprises", and has reference significance for noise control engineering.

[Application status of CFD technology in occupational hazard control].

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.

[Kindlin-2 regulates endometrium development via mTOR and Hippo signaling pathways in mice].

OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool mice and Kindlin-2flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. RESULTS: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. CONCLUSION: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.

[Epidemiological characteristics of local COVID-19 epidemics and control experience in routine prevention and control phase in China].

The COVID-19 pandemic is still ongoing in the world, the risk of COVID-19 spread from other countries or in the country will exist for a long term in China. In the routine prevention and control phase, a number of local COVID-19 epidemics have occurred in China, most COVID-19 cases were sporadic ones, but a few case clusters or outbreaks were reported. Winter and spring were the seasons with high incidences of the epidemics; border and port cities had higher risk for outbreaks. Active surveillance in key populations was an effective way for the early detection of the epidemics. Through a series of comprehensive prevention and control measures, including mass nucleic acid screening, close contact tracing and isolation, classified management of areas and groups at risk, wider social distancing and strict travel management, the local COVID-19 epidemics have been quickly and effectively controlled. The experiences obtained in the control of the local epidemics would benefit the routine prevention and control of COVID-19 in China. The occurrence of a series of COVID-19 case clusters or outbreaks has revealed the weakness or deficiencies in the COVID-19 prevention and control in China, so this paper suggests some measures for the improvement of the future prevention and control of COVID-19.

[Investigating the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of severe scald rabbits based on 16S ribosomal RNA high-throughput sequencing].

Objective: To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods: The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1st, 3rd, and 7th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and ß diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results: Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping and scald+medium-dose group on the 1st and 3rd day after grouping were all significantly increased (P<0.01), the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping, and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7th day after grouping and scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and scald+high-dose group on the 3rd and 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and in scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+high-dose group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 1st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3rd and 7th day after grouping and in normal control group on the 3rd day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group both on the 3rd and 7th day after grouping were significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7th day after grouping and scald+medium-dose group both on the 3rd and 7th day after grouping were significantly increased (P<0.05 or P<0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3rd and 7th day after grouping and in scald+medium-dose group on the 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the level of IL-1ß in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7th day after grouping was significantly decreased (P<0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 3rd day after grouping, the levels of TNF-α and IL-1ß in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly decreased (P<0.05), and the levels of IL-1ß in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7th day after grouping were significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). On the 7th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes, Clostridium and Bacteroidetes, Clostridium and Bacteroidetes, Rumenobacteriaceae and Clostridium and Bacteroideaceae, Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices (P>0.05), and no obvious difference in ß diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions: After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

[Study on the diffusion of hydrogen fluoride in an electrolytic fluoride plant based on CFD numerical simulation method].

Objective: Using CFD technology to grasp the distribution and diffusion of hydrogen fluoride in an electrolytic fluorine plant, provide guidance and scientific basis for enterprises to carry out occupational health management in enterprises, install hazardous substance alarm devices, and protect workers' occupational health. Methods: In July 2019, the diffusion law of hydrogen fluoride gas produced in an electrolytic fluorine plant is selected as the research object. Through the establishment of models and grids, the Fluent numerical simulation method is finally used to simulate the diffusion and distribution of hydrogen fluoride gas under ventilation conditions. Results: The results showed that the average concentration of hydrogen fluoride was 0.045 mg/m(3) in the workplace, and the absorbed zone height (1.5 m) was 0.02 mg/m(3) in the inspection channel, which was in accordance with the national standard. However, there is eddy current above the electrolyzer near the inlet, may lead to the accumulation of hydrogen fluoride gas. Conclusion: The research of CFD numerical simulation method on the distribution and diffusion of hydrogen fluoride concentration in electrolytic fluorine plant can be applied to the prevention, control and management of occupational hazards in electrolytic fluorine plant.

[MYC and BCL-2 protein co-expression and prognosis of patients with diffuse large B-cell lymphoma: a propensity score matching analysis].

Objective: We investigated the impact of MYC/BCL-2 protein co-expression on the prognosis of diffuse large B-cell lymphoma (DLBCL) patients and observed whether double expression (DE) remains an independent poor prognostic factor in DLBCL after the addition of therapeutic factors such as DA-EPOCH-R, central prophylaxis, and transplantation. Methods: Available pathological findings were retrospectively collected from 223 DLBCL patients at the Peking Union Medical College Hospital from 2015 to 2018. Seventy-five patients with high MYC/BCL-2 expression were categorized as the DE group. From the 148 non-DE patients, 75 DLBCL patients were selected as the control group, using a 1∶1 matching on propensity scores for age, international prognostic index score, treatment choice, and etc. The differences in overall survival (OS) and progression-free survival (PFS) between the two groups were compared. Results: The 3-year OS was (69.8±5.5) % for the DE group and (77.0±4.9) % for the non-DE group (P=0.225) , while the 3-year PFS was (60.7±5.8) % and (65.3±5.5) % , respectively (P=0.390) . Subgroup analysis in patients treated with the R-CHOP regimen revealed that for the DE and non-DE patients, the 3-year OS was (61.3±7.5) % and (77.2±5.6) % (P=0.027) , and the 3-year PFS was (52.1±7.5) % and (70.6±6.0) % (P=0.040) , respectively. Multivariate analysis showed that age, stage of Ann Arbor, COO staging, whether central prophylaxis was performed, and whether transplantation was performed were significant independent risk factors of the prognosis of DLBCL patients (P<0.05) . On the other hand, MYC/BCL-2 protein double expression was not significantly associated with prognostic outcomes. Conclusion: MYC/BCL-2 protein double expression was significantly associated with poor prognosis under R-CHOP regimen treatment, but the poor prognostic impact of DE on DLBCL was eliminated under intensive regimens such as DA-EPOCH-R and transplantation.

Standard diffusion-weighted, intravoxel incoherent motion, and dynamic contrast-enhanced MRI of musculoskeletal tumours: correlations with Ki67 proliferation status.

AIM: To determine whether quantitative parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with the Ki67 proliferation status in musculoskeletal tumours. MATERIALS AND METHODS: Twenty-eight patients with musculoskeletal tumours diagnosed via surgical specimen histological analysis who underwent standard DWI, IVIM, and DCE were reviewed retrospectively. The mean standard DWI (apparent diffusion coefficient [ADC]), IVIM (pure diffusion coefficient [D], pseudo-diffusion coefficient [D∗] and perfusion fraction [ƒ]), and DCE (volume transfer constant [Ktrans], rate constant [Kep], and extravascular extracellular volume fraction [Ve]) parameters were measured and correlated with the Ki67 index. The Ki67 value was categorised as high (>20%) or low (≤20%). RESULTS: The ADC and D values correlated negatively with the Ki67 index (r=-0.711∼-0.699, p<0.001), whereas the Ktrans and Kep values correlated positively with the Ki67 index (r=0.389-0.434, p=0.021, 0.041). The ADC and D values were lower (p<0.001), whereas the Ktrans and Kep values were higher (p=0.011, 0.005) in musculoskeletal tumours with a high Ki67 status than in those in a low status. The ADC and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.953), which is statistically bigger than the AUC of Ktrans and Kep (0.784 and 0.802, respectively). CONCLUSION: ADC, D, Ktrans, and Kep correlate with the Ki67 index. ADC and D are the strongest quantitative parameters for predicting Ki67 status.

Inhibition of carbonic anhydrase II by sulfonamide derivatives.

A series of sulfonamide derivatives were synthesized, and the enzyme inhibitory activity of the synthesized compounds on carbonic anhydrase II was evaluated. Through molecular docking studies, it was found that compounds 1b, 1e, 2a, 2b, 3a have a strong binding affinity to carbonic anhydrase II. The IC50 values of the four compounds 1e, 2b, 3a, and 3b were lower than that of the positive control drug acetazolamide. What's more, the compounds had a high inhibitory activity for A549 lung cancer cell growth, among them, 1e and 3a could inhibit both carbonic anhydrase II and lung cancer cell proliferation.

[A comparison between endoscopic CO2 laser cauterization and open neck surgery in the treatment of congenital piriform fistula].

Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO2 laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO2 laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.

[Salvianolic acid B and its magnesium salt inhibit SARS-CoV-2 infection of Vero-E6 cells by blocking spike protein-mediated membrane fusion].

OBJECTIVE: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infection in vitro and explore the molecular mechanism. OBJECTIVE: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Circular dichroism spectroscopy was used to examine the structural characteristics of HR1 and HR2 regions of SARS-CoV-2 S protein, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of Sal-B on virus-cell membrane fusion. Flow cytometry was carried out to analyze the effect of Sal-B on the binding of SARS-CoV-2 RBD to hACE2 receptor. OBJECTIVE: The median effective concentrations (EC50) of Sal-B and ZDDY against SARSCoV-2 infection in Vero-E6 cells were 55.47 µmol/L and 36.07 µg/mL, respectively. Both Sal-B and ZDDY successfully inhibited the entry of SARS-CoV-2 pseudovirus into the cells that stably expressed human ACE2 (ACE2/293T), with half maximal inhibitory concentrations (IC50) of 1.69 µmol/L and 24.81 µg/mL, respectively. Sal-B showed a binding affinity of -8.2 kcal/mol to the 6-helix bundle (6-HB) of SARS-CoV-2 S protein. Molecular dynamics simulation showed stable binding between Sal-B and the 6-HB of SARS-CoV-2 S protein at the predicted binding site. Sal-B disturbed the formation of the secondary structure of 6-HB in HR1P/HR2P mixture, resulting in a significantly lowered α-helicity (P < 0.05). Sal-B dose-dependently inhibited SARS-CoV-2 S protein-mediated cell-cell fusion, with an IC50 of 3.33 µmol/L. Sal-B showed no effect on RBD-Fc protein binding to the ACE2 receptor. OBJECTIVE: Sal-B and its magnesium salt ZDDY can inhibit the entry of SARS-CoV-2 in Vero-E6 cells in vitro by blocking SARS-CoV-2 spike protein-mediated virus-cell membrane fusion.

Machine learning-based radiomic evaluation of treatment response prediction in glioblastoma.

AIM: To investigate machine learning based models combining clinical, radiomic, and molecular information to distinguish between early true progression (tPD) and pseudoprogression (psPD) in patients with glioblastoma. MATERIALS AND METHODS: A retrospective analysis was undertaken of 76 patients (46 tPD, 30 psPD) with early enhancing disease following chemoradiotherapy for glioblastoma. Outcome was determined on follow-up until 6 months post-chemoradiotherapy. Models comprised clinical characteristics, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and 307 quantitative imaging features extracted from enhancing disease and perilesional oedema masks on early post-chemoradiotherapy contrast-enhanced T1-weighted imaging, T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Feature selection was performed within bootstrapped cross-validated recursive feature elimination with a random forest algorithm. Naive Bayes five-fold cross-validation was used to validate the final model. RESULTS: Top selected features included age, MGMT promoter methylation status, two shape-based features from the enhancing disease mask, three radiomic features from the enhancing disease mask on ADC, and one radiomic feature from the perilesional oedema mask on T2WI. The final model had an area under the receiver operating characteristics curve (AUC) of 0.80, sensitivity 78.2%, specificity 66.7%, and accuracy of 73.7%. CONCLUSION: Incorporating a machine learning-based approach using quantitative radiomic features from standard-of-care magnetic resonance imaging (MRI), in combination with clinical characteristics and MGMT promoter methylation status has a complementary effect and improves model performance for early prediction of glioblastoma treatment response.

[Effect of alprostadil in early wound healing of rats with deep partial-thickness scald].

Objective: To explore the effect of alprostadil in early wound healing of rats with deep partial-thickness scald. Methods: Ninety specific pathogen free healthy Sprague-Dawley rats (half males and half females) were divided into sham scald group, simple scald group, and alprostadil group using the random number table with 30 rats in each group. Rats in sham scald group were sham injured, and rats in the other 2 groups were inflicted with deep partial-thickness scald of 30% total body surface area on the back. Immediately after scald, rats in the 3 groups received anti-shock treatment. Two hours post scald, rats in sham scald group and simple scald group were injected intraperitoneally with 1 mL normal saline, and rats in alprostadil group were injected intraperitoneally with 1 mL alprostadil injection, once a day and continued for 14 days. On post scald day (PSD) 3, 7, and 14, 10 rats in each group were collected for observing the general wound conditions and the wound healing rates of rats in 2 scald groups were calculated, abdominal aortic blood of 2 mL from each rat were collected to detect serum thromboxane B2 by enzyme-linked immunosorbent assay, and wound tissue on the back was collected to examine pathomorphological change by hematoxylin-eosin staining and to detect wound microvessel density (MVD) by immunohistochemical staining. Data were statistically analyzed with analysis of variance of factorial design, t test, Kruskal-Wallis H test, Mann-Whitney U test, and Bonferroni correction. Results: (1) There was no scald wound in rats in sham scald group. On PSD 3, wounds of rats in simple scald group and alprostadil group formed dry eschar. On PSD 7 and 14, wound areas of rats in alprostadil group were significantly smaller than those of rats in simple scald group, and with less exudation. (2) On PSD 3, the wound healing rates of rats in simple scald group and alprostadil group were similar (t=1.167, P>0.05). On PSD 7 and 14, the wound healing rates of rats in alprostadil group were significantly higher than those in simple scald group (t=8.657, 33.050, P<0.01). (3) On PSD 3, 7, and 14, the levels of serum thromboxane B2 of rats in simple scald group and alprostadil group were (541±22), (607±47), (688±21), (326±25), (271±21), (135±27) pg/mL, significantly higher than (17±6), (16±4), (16±4) pg/mL of rats in sham scald group (t=72.977, 39.685, 102.076, 37.033, 37.253, 13.845, P<0.01). On PSD 3, 7, and 14, the levels of serum thromboxane B2 of rats in alprostadil group were significantly lower than those in simple scald group (t=20.637, 20.651, 51.680, P<0.01). (4) Normal epidermis and dermis were seen in rats in sham scald group. On PSD 3, a large number of necrotic tissue and inflammatory cells infiltration were seen in wounds of rats in simple scald group, while a little new epithelium formation and some inflammatory cells infiltration were seen in wounds of rats in alprostadil group. On PSD 7 and 14, the new epithelium of rats in alprostadil group was significantly thicker than that in simple scald group, and epidermis formed gradually in alprostadil group. (5) On PSD 3, 7, and 14, the wound MVD of rats in simple scald group and alprostadil group were significantly higher than those in sham scald group (Z=-3.780, -3.781, -3.780, -3.780, -3.781, -3.780, P<0.01). On PSD 3, the wound MVD of rats in simple scald group and alprostadil group were similar (Z=-1.965, P>0.05). On PSD 7 and 14, the wound MVD of rats in alprostadil group were significantly higher than those in simple scald group (Z=-3.780, -3.780, P<0.01). Conclusions: The early intervention with alprostadil can significantly improve microcirculation of deep partial-thickness scald wound, reduce inflammatory cell infiltration, promote the formation of new blood vessels, thus promoting wound healing.

[Predictive values of routine blood test results for iron deficiency in children].

Objective: To explore the predictive values of routine blood test results for iron deficiency (ID) screening in children. Methods: Routine blood test results and serum ferritin (SF) levels from 1 443 healthy children (862 boys, 581 girls) aged 6 months to 18 years, who were seen for well-child visits between June 2017 and May 2019 in Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. ID was defined as SF<20 µg/L, iron deficiency anemia (IDA) as ID with anemia (hemoglobin(Hb)<110 g/L at 6 months-5 years of age, Hb<120 g/L at 6-18 years of age), non-anemia ID as ID without anemia, non-ID anemia as SF≥20 µg/L with anemia, and healthy control subjects as those with SF≥20 µg/L but without anemia. The blood test results including Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), and the percentage of low hemoglobin density (LHD) of healthy control, non-anemia ID, non-ID anemia, and IDA groups were compared by analysis of variance (ANOVA) or non-parametric test, quantitative data were described as x±s or M(interquartile range), and receiver operating characteristic curve (ROC) analysis was applied to assess predictive values of routine blood test results and LHD for detecting IDA and ID. Results: Among 1 443 children with median age of 2.1(3.3) years, 1 061 children were in healthy control group, 292 in non-anemia ID group, 43 in non-ID anemia group and 47 in IDA group. The prevalence of ID was much higher than that of anemia (23.5% (339/1 443) vs. 6.2% (90/1 443) , χ(2)=169.76, P<0.01). Compared with control group, non-anemia ID group showed higher LHD (0.088 (0.093) vs.0.073 (0.068), P<0.01) and RDW (0.131±0.013 vs. 0.126±0.008, P<0.01), lower MCV ((80±4) vs. (83±4) fl, P<0.01) and MCHC values ((326±9) vs. (329±8) g/L, P<0.01). IDA group showed higher LHD (0.322(0.544)) and RDW (0.151±0.018), lower MCV ((73±6) fl) and MCHC values((309±14) g/L) than non-anemia ID group (all P<0.01). The area under curve (AUC) values of MCHC, LHD, RDW and MCV for detecting ID were 0.63 (95%CI: 0.60-0.67), 0.63 (95%CI:0.60-0.67), 0.67 (95%CI: 0.63-0.70) and 0.73 (95%CI: 0.69-0.76) respectively. With cutoff limits (MCV<80.2 fl, RDW>0.131 or MCHC<322 g/L), MCV, RDW and MCHC showed higher sensitivity for screening ID than hemoglobin (0.540, 0.469 and 0.336 vs. 0.139, χ(2)=121.70, 87.47, 35.56, all P<0.01). Conclusion: MCV, RDW and MCHC can be used to screen ID in primary health care settings.