Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Ferroptosis is a way of cell death with lipid peroxides as the core.Cells can reduce ferroptosis sensitivity by relying on glutathione peroxidase 4(GPX4)/glutathione(GSH)antioxidant systems.Triple-negative breast cancer(TNBC)cells are more dependent on the intracellular antioxidant mechanism than normal cells,thus induction of ferroptosis based on the GPX4/GSH system has shown bright anti-TNBC prospects.This paper reviews the recent research on TNBC treatment with ferroptosis in the background of GPX4/GSH,in order to provide references for the clinical treatment of TNBC.

Objective:To compare the efficacy of modified "double flaps" pyeloplasty and traditional dismembered pyeloplasty in the treatment of special types of hydronephrosis with small pelvis and long proximal ureteral stricture in children.Methods:The data of 39 children with special types of hydronephrosis treated in Seventh Medical Center, General Hospital of PLA from June 2018 to June 2019 were retrospectively analyzed. Among them, 33 were boys and 6 were girls. The median age of the patients was 12.0(4.5, 63.5) months. Nine of them had left hydronephrosis and four children had right hydronephrosis. These patients with small pelvis existed the characteristics that the anteroposterior diameter of pelvis was smaller than 2.5 cm and these patients existed the symptom of hematuria, flank pain or recurrent urinary tract infection with the imaging revealing ureteral obstruction. The length of proximal ureteral stenosis ranged from 2.0 to 4.0 cm. Among 39 cases, 19 cases were operated with modified "double flaps" pyeloplasty, which was the modified "double flaps" pyeloplasty group. 20 cases were operated with traditional Anderson-Hynes pyeloplasty, which was traditional pyeloplasty group. The technique of modified "double flaps" pyeloplasty mainly included that the renal pelvis was cut into double flaps, the inferior flap was anastomosed with the spatulated ureter and the superior was covered, so that the length and caliber of the ureter were partial extended. The median age of two groups were 12.0 (6.0, 44.0) months and 12.0 (4.8, 62.8) months respectively, the anterior and posterior diameter of renal pelvis were (2.8±0.8)cm and (2.6±0.6)cm respectively, and split renal function were (36.7±5.1)% and (36.0±6.8)% respectively. There were no statistically significant differences in above parameters between the two groups( P>0.05). The clinical efficacy of the two groups were compared by collecting and comparing the operation related data and postoperative follow-up data. Results:The operation of 39 children in this study was successfully completed without conversion to open surgery.The operation time of "double flap" pyeloplasty group and traditional pyeloplasty group were (142.6±9.6) min and (124.5±8.6) min respectively, and the intraoperative anastomosis time were (56.1±7.2) min and (47.6±4.8) min respectively. There were significant difference in operation time and intraoperative anastomosis time between the two groups( P<0.05). Thirty-nine children were followed up normally without loss. The mean follow-up time was (27.7±2.5) months after surgery. In the "double flaps" pyeloplasty group, 2 cases suffered with fever who were diagnosed as urinary tract infection and improved after antibiotic treatment. In the traditional pyeloplasty group, 2 cases suffered with fever who were diagnosed as urinary tract infection and improved after antibiotic treatment. Two children had flank pain during follow-up to more than one year and the examination revealed that the anteroposterior diameter of the renal pelvis gradually increased. So surgery were performed again and the two children recovered. There were no significant differences in complication rate (2/19 and 4/20) and short-term surgical success rate(19/19 and 18/20) between the two groups ( P>0.05). Conclusions:The operation time and anastomosis time of the modified "double flap" technique for treating hydronephrosis are longer than those of the traditional method. But in the treatment of special types of hydronephrosis with small renal pelvis or long proximal ureteral stricture, it may have application prospects in reducing complications.

Objective:To investigate the similarities and differences of Doppler echocardiographic parameters in healthy adults among Chinese (EMINCA study), Japanese (JAMP study) and Europeans (NORRE study).Methods:Based on the published Doppler echocardiographic data of JAMP and NORRE studies, the corresponding Doppler parameters were selected from the original database of EMINCA study and stratified by sex and age groups accordingly. Independent-samples t-test, summary t-test, and one-way analysis of variance (ANOVA) were used to test the differences between groups. Results:①Common Doppler parameters in three studies included: peak velocities of early diastolic (E) and late diastolic waves (A) of mitral valve inflow, E/A ratio, deceleration time (DT) of E wave, tissue velocities of early diastole (e′ ) and late diastole (a′ ) at both septal and lateral sites of the mitral annulus and the average value of e′ at both sites (average-e′), ratios of E to septal e′ (septal-E/e′), E to lateral e′ (lateral-E/e′), and E to average e′ (average-E/e′). ②Differences between genders: There existed significant gender differences for 5/10 of parameters in EMINCA study, 8/10 in JAMP study and 3/12 in NORRE study (all P<0.05). ③Stratification by sex and age groups: Except for DT for men in EMINCA study, significant differences were found in all 12 Doppler parameters both for men and women in all three studies (all P<0.05). ④Comparison between EMINCA and JAMP studies: There were statistically significant differences in 8/10 and 9/10 of parameters for men and women, respectively (all P<0.05). ⑤Comparison between EMINCA and NORRE studies: 7/12 of parameters both in men and women were significantly different between the two studies (all P<0.05). ⑥For the three studies, 6/10 of parameters both in men and women correlated positively with age ( r=0.12-0.66, all P<0.001), while 4/10 correlated negatively with age ( r=-0.27--0.72, all P<0.001). Conclusions:Doppler echocardiographic measurements in healthy adults are significantly different with genders, ages and races/nationalities. Therefore, gender, age and race/nationality-specific reference values of Doppler echocardiography parameters should be encouraged in clinical practice.

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.

Objective:To investigate the efficiency of deep learning image reconstruction (DLIR) algorithm in the image quality and detection of hypovascular hepatic metastases under low radiation doses in comparison with adaptive statistical iterative construction-V (ASiR-V).Methods:Fifty-six patients with suspected hypovascular hepatic metastases who needed abdominal enhanced CT scans were collected prospectively in the First Affiliated Hospital of Zhengzhou University from January to April 2021. The patients received conventional radiation dose with tube current-time products of 400 mA CT scans in the first venous phase, low-dose CT scans in the second venous phase, which were set as tube current-time products of 280 mA for group A (19 cases), 200 mA for group B (19 cases) and 120 mA for group C (18 case), respectively. The images of first venous phase and 3 groups of second venous phase were both reconstructed with ASiR-V60% and high-DLIR (DLIR-H). Quantitative parameters [image noise, liver and portal vein signal to noise ratio (SNR), contrast to noise ratio (CNR)] and qualitative parameters (overall image quality, lesion conspicuity, diagnostic confidence) were compared between ASiR-V60% and DLIR-H images, and the effective radiation dose (ED) and the lesion detectability of each group was recorded. The paired t test was used to compare quantitative parameters, whereas the Wilcoxon signed-rank test of paired data was used to compare qualitative parameters. Results:In the second venous phase, ED was (5.56±0.35) mSv in group A, (3.88±0.23) mSv in group B, and (2.42±0.23) mSv in group C, with a decrease of 30%, 50% and 70% compared with the first venous phase, respectively. Moreover, with the decrease of radiation dose, the noise gradually increased, and the CNR lesions, SNR liver and SNR portal vein all gradually decreased. DLIR-H images had statistically better quantitative scores than ASiR-V60% images when the same radiation dose was applied (all P<0.001). Furthermore, the qualitative parameters of each group decreased with the decrease of radiation dose. Under the same radiation dose, the overall image quality, lesion conspicuity and diagnostic confidence of DLIR-H were higher than those of ASiR-V60% (all P<0.001). All lesions [100% (84/84)] were detected by ASIR-V60% and DLIR-H in group A, 92.0% (75/81) in group B, and 88.0% (79/89) in group C. Conclusions:Compared with ASiR-V60%, DLIR-H could reduce image noise, improve overall image quality and lesion conspicuity of hypovascular hepatic metastases as well as increase diagnostic confidence under different radiation doses.

This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

PLZ-NPs (PNS-lipid-zein nanoparticles) prepared by co-assembly of Panax notoginseng saponins, lecithin, β-sitosterol and zein were applied for in vitro cell experiment and oral gavage to study the protective effect of cerebral ischemia-reperfusion rats.PLZ-NPs were characterized by Malvin-particle size analyzer and transmission electron microscope (TEM), respectively. The toxicity of PLZ-NPs and free carrier were evaluated by MTT, and the uptake of nanoparticles in Caco-2 cells was analyzed by laser confocal and flow cytometry. The cerebral ischemia reperfusion rat model was established by MCAO method and then be given samples by gavage for 3 days. The brain tissues were taken to stain by 2, 3, 5-triphenyltetrazole chloride (TTC) and the biochemical indicators of MDA, inflammatory cytokines IL-1β and TNF-α, apoptosis-related proteins Bax and Bcl-2 from the harvested brain tissues were detected to evaluate the protective effect of PNS in PLZ-NPs on cerebral ischemia reperfusion. The particle size, PDI, and zeta potential of formed PLZ-NPs were (116.4 ± 0.81) nm, 0.048 and -(31.5 ± 0.31) mV, respectively. The results of MTT showed that the zein lipoprotein carrier was non-toxic to Caco-2 cells. The results of laser confocal and flow cytometry showed that FITC uptake of nanoparticles could be significantly improved in Caco-2 cells.The uptake from the nanoparticles at 4h was 1.76 times of that of the free FITC group.Compared with the model group, the TTC staining images of free drug PNS group and PLZ-NPs group showed certain reduction in the white infarct area.The contents of MDA, IL-1β, TNF-α and Bax were significantly decreased, while the content of Bcl-2 was significantly increased. Furthermore, all parameters of PLZ-NPs group showed better results than those of PNS group, and there was a significant difference (P < 0.05). All results indicated that the prepared PLZ-NPs had good stability and biological safety, and could significantly increase the uptake in intestinal epithelial cells, and effectively protect against the damage caused by cerebral ischemia reperfusion in rats.