Objective:To analyze the epidemiological characteristics of respiratory syncytial virus (RSV) among children in Hebei from 2019 to 2023.Methods:A total of 46 576 lower respiratory tract specimens were collected from hospitalized children in the Children′s Hospital of Hebei Province from 2019 to 2023. Multiple RT-PCR and capillary electrophoresis were used to detect 13 common respiratory pathogens in the specimens, and the results were statistically analyzed.Results:The overall positive rate of RSV was 18.76%(8 739/46 576). The overall positive rates of RSV in male and female children were 18.84%(5 174/27 462) and 18.65%(3 565/19 114), respectively, showing no statistically significant difference between genders (χ 2=0.916, P=0.339). A linear relationship was found between the positive rate of RSV and age ( P<0.01). There was a significant difference in the positive rates of RSV in different years (χ 2=723.71, P<0.01). The positive rate of RSV peaked in the period from December to February from 2019 to 2021. In 2019 and 2020, the positive rates of RSV were very low from May to October, while the positive rate of RSV was above 10% throughout the whole year of 2021 and small off-season epidemics occurred in May and August. The positive rate of RSV was low in 2022, and no significant seasonal change was observed. The rate of RSV infections peaked from April to June in 2023. There were significant differences in the rates of RSV infections before, during and after the COVID-19 epidemic in each age group ( P<0.01). The rate of mixed infections was 29.20%(2 522/8 739), and the most common other respiratory pathogen was human rhinovirus (52.29%, 1 342/2 552 ). Conclusions:RSV is a common pathogen causing respiratory tract infections in children in Hebei, especially in children under 3 years old. After the COVID-19 epidemic, there are off-season RSV epidemics. Given the variations in the epidemiological features of RSV, it is necessary to carry out continuous monitoring of RSV to provide scientific data for the prevention and control of related diseases.

OBJECTIVE To establish an HPLC method for the separation of enantiomers of farrerol, and apply it to the determination of the content of enantiomers in Rhododendri Daurici Folium and Rhododendron Micranthum. METHODS HPLC was used to separate the farrerol enantiomers, and the chromatographic conditions of chiral column type, mobile phase ratio, flow rate, and column temperature were optimized. The thermodynamic separation of farrerol enantiomers was discussed. Thermodynamic parameters such as enthalpy change, entropy change, enthalpy change and entropy change were calculated. And the contents of two enantiomers in Rhododendri Daurici Folium and Rhododendron Micranthum were determined under the optimum resolution conditions. RESULTS The optimum separation conditions for two enantiomers of farrerol were determined as follows: Chiralcel OJ-RH(4.6 mm×150 mm, 5 μm), equilibrium elution of acetonitrile-water(40∶60), the flow rate of 0.5 mL·min–1, the column temperature of 25 ℃, and the detection wavelength of 295 nm. Under the optimum separation conditions, the resolution of farrerol enantiomers reached 1.5, indicating that the two enantiomers of the farrerol could be completely separated. When the column temperature was between 20 ℃ and 35 ℃, the separation factor decreased with the increase of temperature. The lnα of the two enantiomers of farrerol showed a good linear relationship with 1/T, and the chiral reselution process was controlled by enthalpy. The enantiomer separation method of farrerol was applied to the determination of farrerol enantiomer in Chinese medicinal materials of Rhododendri Daurici Folium and Rhododendron Micranthum. The linear relationship between the two enantiomers of farrerol were good in the range of 0.718–57.44 μg·mL–1 and 1.28–102.24 μg·mL–1, respectively. And the contents of the two enantiomers of farrerol in Rhododendri Daurici Folium were 0.228 2 and 0.466 2 mg·g–1, respectively. And the contents of the two enantiomers of farrerol in Rhododendron Micranthum were 0.416 8 and 0.707 3 mg·g–1, respectively. CONCLUSION This method is simple, efficient and suitable for the determination of farrerol enantiomers in traditional Chinese medicine.

Objective:To investigate the urinary sediment findings and the clinicopathologic features of IgA nephropathy (IgAN) patients with acute kidney injury (AKI).Methods:It was a retrospective study. The patients with renal biopsy-proven primary IgAN in Peking University First Hospital from January 31, 2013 to July 31, 2015 were selected. According to whether AKI occurred at renal biopsy or not, the patients were divided into AKI group and non-AKI group. Morning urine samples were obtained on the day of renal biopsy. Urine sediments, including various cells and casts, were examined. The clinical data, urinary sediments, and renal pathological changes were compared between the two groups. Logistic regression analysis was performed to identify the association between clinical pathological changes, urinary sediment indicators and AKI, or clinical pathological changes and urinary sediment indicators.Results:There were 502 IgAN patients enrolled in this study, with age of (36.1±12.1) years old and 261 males (52.0%). The incidence of AKI was 11.4% (57/502) among the enrolled patients at the time of renal biopsy. Common causes of AKI included gross hematuria-induced AKI (10 cases), acute tubulointerstitial nephritis (10 cases), crescentic IgAN (9 cases), malignant hypertensive renal damage (6 cases), and multiple etioloqy or unknown etiology (22 cases). Compared with non-AKI group, AKI group had higher proportions of males and malignant hypertension, higher levels of proteinuria and urinary erythrocyte counts, and higher frequencies of gross hematuria, leukocyturia, renal tubular epithelial cells, and granular casts (all P<0.05). AKI group also had higher proportions of severe tubular atrophy/interstitial fibrosis (T2) and cellular/cellular fibrous crescent formation (C2) than non-AKI group (both P<0.05). Logistic regression analysis results showed that, there were statistically significant differences in the correlation between AKI and gender, 24 h urinary protein, urinary erythrocyte counts, granular casts and renal tubular atrophy/interstitial fibrosis (T) scores (all P<0.05). Hematuria, leukocyturia, red blood cell casts, white blood cell casts, granular casts, and fatty casts were correlated with endothelial hypercellularity (E) and cellular/cellular fibrous crescent formation (C) scores, respectively (all P<0.05). Hematuria was correlated with mesangial hypercellularity (M) scores ( OR=2.613, 95% CI 1.520-4.493, P=0.001). Hematuria ( OR=1.723, 95% CI 1.017-2.919, P=0.043) and fatty casts ( OR=2.646, 95% CI 1.122-6.238, P=0.026) were correlated with segmental sclerosis or adhesion (S) scores. Leukocyturia ( OR=1.645, 95% CI 1.154-2.347, P=0.006) and fatty casts ( OR=2.344, 95% CI 1.202-4.572, P=0.012) were correlated with T scores. Epithelial cell cast was correlated with C scores ( OR=1.857, 95% CI 1.174-2.939, P=0.008). Conclusions:AKI is a common complication among IgAN patients with diverse etiology and more severe clinicopathological features. Urinary sediment findings can reflect renal pathological changes to some extent, and therefore assist in the clinical diagnosis and treatment of IgAN patients with AKI.

Objective To investigate the levels of γδ T cells and their subpopulations in bone marrow(BM)of patients with myelodysplastic syndrome(MDS),it aims to explore the immune deficiency status of BM microenvi-ronment in MDS patients.Methods BM samples were collected from MDS patients before and after treatment,as well as from normal donors.Multicolor flow cytometry was utilized to detect bone marrow γδ T cells and subpopulation levels.The changes of the T cell subsets after treatment were also analyzed.Results The levels of BM γδ T cells and follicular helper γδ T cells from MDS patients were significantly lower than those of normal donors(P<0.05).Among γδ T cells at different stages of differentiation,only the frequencies of na?ve γδ T cells from MDS patients decreased significantly(P = 0.037),and there was no significant difference observed about central memory,effector memory,and terminally differentiated γδ T cells in MDS patients compared to normal donors(P>0.05).Although there was a slight decrease in PD1+γδ T cells and an increase in TIM3+γδ T cells,these differences were not statistically significant(P>0.05).In patients who achieved a curative effect,the proportions of γδ T cells and naive γδ T cells increased significantly after treatment,and the effector memory γδ T cells decreased significantly after treatment(P<0.05).After treatment,85.71%(6/7)of MDS patients showed a decrease in γδ+TIM3+ T cell levels to varying degrees.Conclusions The levels of γδ T cells and their subpopulations in the BM microenvironment of patients with MDS exhibit varying degrees of abnormalities.However,in patients who receive effective treatment,these abnormal γδ T cells can recover.By detecting the levels of γδ T cells and subpopulations,we can gain insights into the immune deficiency status of MDS.This information might serve as an indicator to assess treatment efficacy and provide valuable insights for anti-tumor immunotherapy.

Objective:To compare the characteristics of corneal stromal demarcation line after different surgical methods of riboflavin/ultraviolet A corneal collagen cross-linking (CXL) in early keratoconus, and analyze the influence of the demarcation line on the cross-linking effect.Methods:A non-randomized controlled clinical study was conducted.Sixty-nine eyes of 69 patients treated with riboflavin/ultraviolet A CXL in the Eye Hospital of Shandong First Medical University from May 2019 to February 2021 were included.According to the cross-linking methods, the patients were divided into epithelium-on treatment group (21 eyes) and epithelium-off treatment group (48 eyes). There were 25 eyes in 5.4 J energy group and 44 eyes in 7.2 J energy group.The morphology and changes of corneal stromal cross-linking reaction (corneal stromal demarcation line) were observed at 2 weeks, 1, 3 and 4 months after operation.Changes in the thinnest corneal thickness (TCT), uncorrected visual acuity (UCVA, LogMAR), best corrected visual acuity (BCVA, LogMAR) and corneal maximum curvature (Kmax) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.2019.05). Written informed consent was obtained from each subject.Results:Of the 69 eyes after operation, 44 eyes (63.77%) had demarcation lines, and 25 eyes (36.23%) had no demarcation lines.The occurrence rate of demarcation lines in the epithelium-on treatment group was 79.17%(38/48), which was significantly higher than 28.57%(6/21) in the epithelium-off treatment group ( χ2=16.186, P<0.01). The occurrence rate of demarcation line in 5.4 J energy group was 72.00%(18/25), and the 7.2 J energy group was 56.80%(25/44), with no significant difference ( χ2=1.565, P=0.302). Slit lamp microscopy and anterior segment-optical coherence tomography showed that the demarcation line appeared at 1-2 weeks after operation, gradually converged and strengthened after 1 month, turned diffuse, blurred and faded by degrees after 2-3 months, and basically disappeared after 4 months.The depth of the demarcation line reached 141-423 μm, with an average depth of (263.44±84.22)μm.Scanning laser confocal microscopy showed that corneal stromal cells were activated and light reflection was enhanced after CXL.Collagen fibers extended vertically and horizontally, crisscrossed, and were in a reticular arrangement.The TCT decreased from preoperative (458.69±38.28)μm to (443.86±36.54)μm at 4 months after operation, showing a statistically significant difference ( t=6.705, P<0.001). There was no significant difference in the TCT reduction between groups with and without demarcation lines ( t=1.684, P=0.100). At 4 months postoperatively, the UCVA of all eyes increased from preoperative 0.74±0.37 to 0.69±0.38, and the difference was statistically significant ( t=2.109, P=0.039). There was no significant difference in BCVA between before and after operation ( t=1.006, P=0.319). There was no significant difference in change of UCVA and BCVA between groups with and without demarcation lines ( t=0.065, P=0.949; t=0.346, P=0.730). There was no significant difference in Kmax in all patients between before and after operation ( t=0.050, P=0.950). There was no significant difference in the Kmax change between groups with and without demarcation lines ( t=-0.739, P=0.464). The change in TCT in the epithelium-off treatment group was significantly greater than that in the epithelium-on treatment group ( t=2.815, P=0.008). There was no significant difference in UCVA, BCVA and Kmax changes between epithelium-on and epithelium-off treatment groups (all at P>0.05). There was no obvious corneal scarring, infectious keratitis, corneal endothelial decompensation or other complications. Conclusions:The demarcation line after CXL may be a sign of the depth of cross-linking reaction, which is more prone to occur after the epithelium-off operation method.Both the epithelium-on and epithelium-off operation methods have similar therapeutic effects.Demarcation line after different cross-linking methods has no significant influence on the cross-linking effect in keratoconus.

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

The interventional therapy of vascular stent implantation is a popular treatment method for cardiovascular stenosis and blockage. However, traditional stent manufacturing methods such as laser cutting are complex and cannot easily manufacture complex structures such as bifurcated stents, while three-dimensional (3D) printing technology provides a new method for manufacturing stents with complex structure and personalized designs. In this paper, a cardiovascular stent was designed, and printed using selective laser melting technology and 316L stainless steel powder of 0-10 µm size. Electrolytic polishing was performed to improve the surface quality of the printed vascular stent, and the expansion behavior of the polished stent was assessed by balloon inflation. The results showed that the newly designed cardiovascular stent could be manufactured by 3D printing technology. Electrolytic polishing removed the attached powder and reduced the surface roughness Ra from 1.36 µm to 0.82 µm. The axial shortening rate of the polished bracket was 4.23% when the outside diameter was expanded from 2.42 mm to 3.63 mm under the pressure of the balloon, and the radial rebound rate was 2.48% after unloading. The radial force of polished stent was 8.32 N. The 3D printed vascular stent can remove the surface powder through electrolytic polishing to improve the surface quality, and show good dilatation performance and radial support performance, which provides a reference for the practical application of 3D printed vascular stent.
Humans ; Stainless Steel ; Powders ; Cardiovascular System ; Constriction, Pathologic

Objective:To explore the effects of intense pulsed light and carbon dioxide fractional laser sequential treatment of early hypertrophic scar after deep burn.Methods:A retrospective cohort study was used. The patients with early hypertrophic scar after deep burn who were admitted to the First People’s Hospital of Zhengzhou from May 2019 to January 2021 and met the inclusion criteria were selected as the study subjects. All patients began to receive sequential laser treatment 4-8 weeks after complete healing of wounds. The treatment method was selected according to the Vancouver scar scale (VSS) score before each treatment. If the blood vessel distribution ≥ 2 points and the thickness<2 points, they were treated with intense pulsed light. If the blood vessel distribution ≥2 points and the thickness ≥ 2 points, they were treated with intense pulsed light combined with carbon dioxide laser. If the blood vessel distribution <2 points and the thickness ≥ 2 points, they were treated with carbon dioxide laser. If the blood vessel distribution < 2 points and the thickness < 2 points, the treatment was ended. Intense pulsed light therapy was performed once a month, and carbon dioxide laser therapy was performed once every 3 months. Before and after treatment, patients were evaluated with VSS, observer scar assessment scale (OSAS) and patient scar assessment scale (PSAS), while higher scores indicated more severe scars. The number of intense pulsed light and carbon dioxide laser treatment during the treatment period, the time of scar formation and the occurrence of complications at the end of the treatment were recorded. SPSS 22.0 software was used for statistical analysis. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare patients before and after treatment. Results:A total of 28 patients were included, including 16 males and 12 females, aged 12-54 years. After the sequential treatment, the VSS scores of color, thickness, vascular distribution, softness and total score were significantly lower than those before the treatment ( t=15.00, 11.90, 15.59, 9.46, 39.24, P<0.001); OSAS scores of vascular distribution, color, thickness, roughness, softness, surface area, overall evaluation and total score were significantly lower than those before treatment ( t=14.89, 10.82, 9.54, 7.23, 16.97, 8.60, 16.42, 25.08, P<0.001); PSAS scores of pain, itching, color, hardness, thickness, irregularity, overall evaluation and total score were significantly lower than those before treatment ( t=26.40, 24.53, 16.54, 12.18, 12.25, 21.04, 22.00, 29.38, P<0.001). During the treatment, the patients were treated with intense pulsed light for (4.00±1.22) times (2-6 times), carbon dioxide laser for (2.54±1.00) times (0-5 times). At the end of the treatment, the scar formation time was (13.82±2.98) months (8-20 months). Complications occurred in 5 cases during treatment and follow-up, including 4 cases of skin blisters and 1 case of infection. No immediate skin lesions, pigmentation, depigmentation, scar aggravation and other adverse reactions occurred. Conclusion:The combination of sequential therapy of intense pulsed light and carbon dioxide laser can significantly improve the appearance and texture of early hypertrophic scar after deep burn, which has good safety.

Objective:To explore the effects of intense pulsed light and carbon dioxide fractional laser sequential treatment of early hypertrophic scar after deep burn.Methods:A retrospective cohort study was used. The patients with early hypertrophic scar after deep burn who were admitted to the First People’s Hospital of Zhengzhou from May 2019 to January 2021 and met the inclusion criteria were selected as the study subjects. All patients began to receive sequential laser treatment 4-8 weeks after complete healing of wounds. The treatment method was selected according to the Vancouver scar scale (VSS) score before each treatment. If the blood vessel distribution ≥ 2 points and the thickness<2 points, they were treated with intense pulsed light. If the blood vessel distribution ≥2 points and the thickness ≥ 2 points, they were treated with intense pulsed light combined with carbon dioxide laser. If the blood vessel distribution <2 points and the thickness ≥ 2 points, they were treated with carbon dioxide laser. If the blood vessel distribution < 2 points and the thickness < 2 points, the treatment was ended. Intense pulsed light therapy was performed once a month, and carbon dioxide laser therapy was performed once every 3 months. Before and after treatment, patients were evaluated with VSS, observer scar assessment scale (OSAS) and patient scar assessment scale (PSAS), while higher scores indicated more severe scars. The number of intense pulsed light and carbon dioxide laser treatment during the treatment period, the time of scar formation and the occurrence of complications at the end of the treatment were recorded. SPSS 22.0 software was used for statistical analysis. Measurement data were expressed as Mean±SD, and paired sample t-test was used to compare patients before and after treatment. Results:A total of 28 patients were included, including 16 males and 12 females, aged 12-54 years. After the sequential treatment, the VSS scores of color, thickness, vascular distribution, softness and total score were significantly lower than those before the treatment ( t=15.00, 11.90, 15.59, 9.46, 39.24, P<0.001); OSAS scores of vascular distribution, color, thickness, roughness, softness, surface area, overall evaluation and total score were significantly lower than those before treatment ( t=14.89, 10.82, 9.54, 7.23, 16.97, 8.60, 16.42, 25.08, P<0.001); PSAS scores of pain, itching, color, hardness, thickness, irregularity, overall evaluation and total score were significantly lower than those before treatment ( t=26.40, 24.53, 16.54, 12.18, 12.25, 21.04, 22.00, 29.38, P<0.001). During the treatment, the patients were treated with intense pulsed light for (4.00±1.22) times (2-6 times), carbon dioxide laser for (2.54±1.00) times (0-5 times). At the end of the treatment, the scar formation time was (13.82±2.98) months (8-20 months). Complications occurred in 5 cases during treatment and follow-up, including 4 cases of skin blisters and 1 case of infection. No immediate skin lesions, pigmentation, depigmentation, scar aggravation and other adverse reactions occurred. Conclusion:The combination of sequential therapy of intense pulsed light and carbon dioxide laser can significantly improve the appearance and texture of early hypertrophic scar after deep burn, which has good safety.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.