Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the relationship between the levels of macrophage migration inhibito-ry factor(MIF),lipoprotein-associated phospholipase A2(Lp-PLA2)and chemokine CC motif ligand 3(CCL3)in peripheral blood and severity of disease and complication of acute kidney injury in neonatal sepsis.Methods A total of 112 children with NS admitted to this hospital from May 2021 to May 2024 were selected as the research objects.According to the neonatal acute physiology score Ⅱ(SNAP-Ⅱ score),they were di-vided into mild group(71 cases)and severe group(41 cases),and according to whether the children were complicated with AKI,they were divided into AKI group(47 cases)and non-AKI group(65 cases).In addi-tion,112 healthy neonates who underwent physical examination in the hospital during the same period were selected as the control group.The levels of MIF,Lp-PLA2 and CCL3 in peripheral blood were detected in each group.Pearson correlation analysis was used to analyze the correlation between the levels of MIF,Lp-PLA2 and CCL3 in peripheral blood and the severity of NS.Multivariate Logistic regression was used to analyze the influencing factors of AKI in children with NS.The receiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of peripheral blood MIF,Lp-PLA2 and CCL3 for the severity of NS and the complication of AKI in NS.Results The levels of MIF,Lp-PLA2 and CCL3 in the severe group were higher than those in the mild group and the control group(P<0.05),and those in the mild group were higher than those in the control group(P<0.05).The severe group had a significantly higher SNAP-Ⅱ score than the mild group(P<0.05).The levels of MIF,Lp-PLA2 and CCL3 in peripheral blood of NS children were posi-tively correlated with SNAP-Ⅱ score(r=0.512,0.463,0.547,P<0.05).The area under the curve(AUC)of peripheral blood MIF,Lp-PLA2 and CCL3 in the diagnosis of severe NS was 0.782,0.772 and 0.753,respec-tively.The AUC of combined diagnosis was 0.888,which was higher than that of individual indicators(P<0.05).The levels of MIF,Lp-PLA2 and CCL3 in AKI group were higher than those in non-AKI group(P<0.05).Neonatal asphyxia,high levels of MIF,Lp-PLA2,and CCL3 were risk factors for AKI in children with NS(P<0.05).The AUC of MIF,Lp-PLA2 and CCL3 in predicting AKI in children with NS were 0.770,0.759 and 0.757,respectively.The AUC of the combined prediction of MIF,Lp-PLA2 and CCL3 was 0.910,which was higher than that of each index alone(P<0.05).Conclusion The levels of MIF,Lp-PLA2 and CCL3 in peripheral blood of children with NS are increased,which are closely related to the aggravation of NS and the development of AKI.The combined detection of MIF,Lp-PLA2 and CCL3 has a high value in the as-sessment of the severity of NS and the risk of AKI.

Objective To investigate the clinical efficacy of Xinxuetong Oral Liquid in the treatment of patients with acute coronary syndrome(ACS).Methods A total of 80 patients with ACS of blood stasis syndrome who were hospitalized in Shunde Hospital of Guangzhou University of Chinese Medicine from January 2023 to September 2023 were randomly divided into the treatment group and control group according to random number table method,40 patients in each group.The patients in the two groups were given conventional western medicine treatment including lifestyle guidance,percutaneous coronary intervention(PCI),and conventional western medicine therapy.Additionally,the treatment group was treated with Xinxuetong Oral Liquid.The course of treatment for the two groups covered eight weeks.Before and after treatment the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,blood stasis syndrome score,angina pectoris score,blood lipid indicators,carotid ultrasonography indicators,echocardiography indicators,and serum levels of trimethylamine-N-oxide(TMAO),nitric oxide(NO),endothelin 1(ET-1),interleukin 8(IL-8),serine/threonine-protein kinase 1(AKT-1),and vascular endothelial growth factor A(VEGF-A).After treatment,the efficacy on TCM syndrome efficacy and the safety of the regimen in the two groups were evaluated.Results(1)During the trial,there were two cases of loss to follow-up and one case of withdrawal due to pneumonia,and eventually a total of 77 patients completed the full course of treatment,among which 39 patients were in the treatment group and 38 patients were in the control group.(2)After eight weeks of treatment,the total effective rate of the treatment group was 89.74％(35/39),and that of the control group was 63.16％(24/38).The intergroup comparison(tested by chi-square test)showed that the effective rate of TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of TCM symptoms such as chest pain,chest distress,symptom aggravation at night,and palpitation in the two groups,as well as the score of gloomy complexion in the treatment group,were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease of scores of chest distress,symptom aggravation at night,and palpitation in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the blood stasis syndrome score and angina pectoris symptom score of the two groups of patients were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the serum TMAO,ET-1,IL-8,AKT-1,and VEGF-A levels in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum NO level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum TMAO,ET-1,IL-8,and AKT-1,VEGF-A levels and the increase of serum NO level in the treatment group were significantly superior to those of the control group(P＜0.05 or P＜0.01).(6)After treatment,the total cholesterol(TCHO)and low-density lipoprotein cholesterol(LDL-C)levels of the two groups(P＜0.01)and the triglyceride(TG)level of the treatment group(P＜0.05)were decreased significantly compared with those before treatment,while the high-density lipoprotein cholesterol(HDL-C)level of the treatment group was increased significantly compared with that before treatment(P＜0.01).No obvious changes of TG and HDL-C levels before and after treatment were shown in the control group(P＞0.05).The comparison of blood lipid indicators after treatment between groups showed that there were no statistically significant differences(P＞0.05).(7)After treatment,the carotid ultrasonography indicators of carotid intima-media thickness(IMT)and Crouse score of the carotid plaque in the two groups were significantly improved compared with those before treatment(P＜0.01).However,there was no statistical significance in the comparison of the two indicators between the two groups after treatment(P＞0.05).(8)The observation of echocardiography indicators showed that only the post-treatment left ventricular diameter(LVd)of the treatment group was significantly larger than that before treatment(P＜0.05),while no obvious changes of the other echocardiography indicators before and after treatment were shown in the two groups(P＞0.05).The comparison between the groups after treatment also showed no statistically significant differences(P＞0.05).(9)During the treatment,no serious drug-induced adverse reactions or drug-related severe cardiovascular events and complications occurred in the two groups.Conclusion The combination of Xinxuetong Oral Liquid with conventional western medicine treatment exerts certain efficacy and safety on improving the clinical symptoms of patients with ACS of blood stasis syndrome,and its therapeutic mechanism may be related to the improvement of blood lipid levels,inflammatory response,and TMAO level.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.

Vitamin D works in the active form 1，25（OH） 2D 3 after binding to vitamin D receptor.Vitamin D deficiency is common in children with renal disease，and the abnormalities of vitamin D and its metabolic pathways are closely related to the occurrence and development of proteinuria and the deterioration of renal function.Vitamin D not only plays its classic role in maintaining calcium and phosphorus homeostasis，but also protects the kidney by improving the immune function of children，blocking the renin-angiotensin-aldosterone system，preventing the occurrence and development of proteinuria，alleviating the damage of podocytes，and delaying renal interstitial fibrosis.Therefore，this article reviews the research progress of vitamin D and its receptor gene polymorphism and kidney disease，in order to serve the clinical practice.

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.
Humans ; Arthritis, Psoriatic/drug therapy* ; East Asian People ; Enthesopathy/complications* ; Registries ; Severity of Illness Index ; Spondylarthritis/epidemiology*

Objective:To investigate the clinical features of pregnant associated Takotsubo cardiomyopathy (PTCM).Methods:We reviewed reported PTCM cases published from January 2007 to June 2022 using the keywords "Tako-tsubo cardiomyopathy""Takotsubo cardiomyopathy" "stress cardiomyopathy" AND "parturition" "pregnancy" "cesarean delivery" "postpartum" "peripartum" "eclampsia" "abortion" in Pubmed and Web of Science databases and the corresponding Chinese words in Wanfang and Chinese Medical Journal Network. Age, obstetric history, mode of delivery, mode of anesthesia, etiological factors, clinical manifestations, treatment, and prognosis of PTCM were recorded. Descriptive statistical analysis was adopted.Results:A total of 55 articles were included, covering 60 patients with PTCM. (1) Age and time of onset: The age of onset was (32.4±6.0) years old. PTCM occurred most frequently during labor [42% (25/60)] and within one day postpartum [32% (19/60)] and during the gestational period [13%(8/60), 33.0 weeks (24.5-37.7 weeks)]. (2) Delivery-related factors: There were 38% (16/42) primiparas and 60% (25/42) multiparas. Among them, 67% (38/57) and 18% (10/57) were delivered by cesarean section and vaginal delivery, respectively. PCTM often lacks obvious triggers [40% (24/60)], with the most common inducing factor being pregnancy-related diseases [27% (16/60)]. (3) Clinical features: The initial symptoms of PTCM were dyspnea [44% (26/59)], followed by chest pain accompanied by dyspnea [17% (10/59)]. The most common subtype of PTCM was the apical type [45% (26/58)], followed by the basal type [24% (14/58)], while the biventricular type was the least common [3% (2/58)] in the PTCM classification. The left ventricular ejection fraction was (31.6±12.1) % at the onset of PTCM, which recovered to (58.2±7.6) % at discharge. PCTM was often complicated by pulmonary edema [67% (40/60)] and cardiogenic shock [55% (33/60)]. (4) Treatment and prognosis: Patients with PCTM usually require noninvasive or invasive ventilator-assisted ventilation [40% (23/58)]. One pregnant woman and five neonates died, while the remaining patients recovered well.Conclusions:PTCM should be considered in differential diagnosis of patients experiencing dyspnea and chest pain during labor and pregnancy. PTCM patients are younger and have more pulmonary edema and cardiogenic shock. Mechanical ventilation is often required, but the prognosis is favorable.