Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective To discuss the clinical application value of super selective renal artery embolization-assisted(SRAE-assisted)laparoscopic partial nephrectomy(LPN).Methods A retrospective analysis of the clinical data of patients with stage T1 renal carcinoma,who received LPN,was conducted.The patients were divided into SRAE group(performing LPN without adopting renal hilum vascular clamping)and VC group(performing LPN with adopting renal hilum vascular clamping).The time spent for operation,amount of intraoperative blood loss,and preoperative and postoperative renal functions were compared between the two groups.According to the warm ischemia time(WIT),the patients of the VC group were subdivided into WIT＜25 min subgroup and WIT≥25 min subgroup,and the preoperative and postoperative renal functions were compared between the two subgroups.Results A total of 59 patients with renal carcinoma were enrolled in this study,including 12 patients in SRAE group and 47 patients in VC group.In VC group,WIT＜25 min subgroup had 33 patients and WIT≥25 min subgroup had 14 patients.In both SRAE group and VC group,no patient was referred to open surgery or total nephrectomy.No patient in SRAE group was referred to traditional LPN.The time spent for operation in SRAE group and VC group was 100.50(73.75,132.50)min and 120.00(90.00,145.00)min respectively,the difference between the two groups was not statistically significant(P＞0.05).The postoperative estimated glomerular filtration rate(eGFR)in SRAE group was 100.56(82.85,106.81),which was remarkably higher than 84.66(70.84,94.85)in VC group(P＜0.05).The postoperative serum creatinine level in VC group was 90.50(77.10,104.90)μmol/L,which was strikingly higher than 72.24(65.97,80.27)μmol/L in SRAE group(P＜0.05).The amount of intraoperative blood loss in SRAE group was 50(50,50)mL,which was lower than 50(50,100)mL in VC group(P＜0.05).In VC group,the postoperative eGFR in WIT≥25 min subgroup was 66.13(47.08,82.50),which was lower than 90.80(77.18,98.78)in WIT＜25 min subgroup(P＜0.05).During the postoperative one-year follow-up,no recurrence was observed in both groups.Conclusion Compared with traditional LPN,SRAE-assisted LPN doesn't need to obstruct the renal hilus during surgery,which can avoid the ischemic impairment of the residual renal function and reduce the amount of intraoperative blood loss,moreover,it doesn't increase the operation time,doesn't increase the incidence of complications such as postoperative bleeding,etc.and doesn't affect the curative efficacy and patient's prognosis.

ObJective·To evaluate the dentofacial phenotype in non-syndromic tooth agenesis(NSTA)patients with paired box gene 9(PAX9)mutation.Methods·Patients with NSTA who visited the Department of Second Dental Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,between January 2016 and December 2023 received whole-exome sequencing to screen PAX9 mutation.The location and number of missing teeth were evaluated by oral pantomography,and dentofacial deformities were evaluated by X-ray cephalometrics.Results·Seven patients with PAX9 mutation were included in the study,including 3 males(42.9％)and 4 females(57.1％).The patients were 7-31 years old at first visit,with a mean age of(19.7±8.0)years old.All the 7 patients were PAX9 heterozygotes,of which 4 were missense and 3 were frameshift.The average number of missing teeth was 15.9±2.9.The number of missing teeth in maxilla(9.6±2.6)was slightly higher than that in mandible(6.3±2.4)(P=0.030).Maxillary second molar(100.0％),maxillary canine(85.7％)and mandibular second premolar(85.7％)were the three most common missing teeth,while mandibular lateral incisor(14.3％)and mandibular canine(14.3％)were the two least missing teeth.Patients with frameshift mutation had more missing teeth(18.3±2.1)than those with missense mutation(14.0±1.8)(P=0.032).X-ray cephalometrics analysis results showed that the angle sella-nasion-subspinale(SNA),angle nasion-subspinale-subspinale-porion(NA-Apo)and sella-nasion(S-N)in adult patients with PAX9 mutation were significantly lower than the normal reference values,suggesting a shorter anterior cranial base and maxillary length.The frankfort horizontal plane-nasion-porion(FH-NPo)was higher than the reference value,and the Y-axis was lower than the reference value,indicating a more prognathic mandible.The angle subspinale-nasion-supramental(ANB)was lower than the reference value,indicating a skeletal angle Ⅲ malocclusion.The angle upper central incisor-nasion-subspinale(angle U1-NA)was higher than the reference value,indicating a lip inclination of maxillary central incisor.The angle lower central incisor-mandibular plane(IMPA)and lower central incisor-nasion-supramental(L1-NB)were lower than the reference values,indicating a retroclination of the mandibular central incisor,and crossbite in the maxillary and mandibular anterior teeth.Conclusion·The dentofacial phenotype of PAX9-mutated patients with NSTA is reported comprehensively.It is helpful to improve the understanding of the role of PAX9 in human maxillofacial development.

Objective:To explore the influence of fentanyl on sorafenib sensitivity in the treatment of hepatocellular carcinoma (HCC) pain.Methods:Adopting a prospective research method, all laboratory tests were conducted in the Central Laboratory of Xinhua Hospital, Dalian University from August 2021 to August 2023. CCK-8 method, clone formation assay and cell counting under light microscope were used to detect cell proliferation of the human liver cancer cell line HepG2. LysoTracker, monodansyl cadaverine and transmission electron microscopy (TEM) were used to detect the levels of autophagy in fentanyl-induced HCC cells. The level of reactive oxygen species was measured using the fluorescent dye, 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Protein immunoblotting test was applied to detect the protein level of upstream protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The effects of the antitumor efficacy of fentanyl combined with sorafenib were evaluated by the HCC tumor-forming experiment in nude mice. Fifteen female BALB/c nude mice (6-week-old) were divided into control group, sorafenib group and sorafenib + fentanyl group by random digits table method with 5 mice each. The nude mice in three groups were subcutaneously injected at left axilla HepG2 cells (4 ×10 6). The nude mice in control group, sorafenib group and sorafenib + fentanyl group were respectively treated with injection of 1 ml of 0.9% sodium chloride, oral sorafenib with 20 mg/kg, oral sorafenib with 20 mg/kg combined with intravenous injection fentanyl with 0.05 mg/kg every other day for 3 consecutive weeks. The tumor volume was measured at the 4th、8th、12th、16th、20th and 24th day. The nude mice were sacrificed after tumors formed and the tumor tissues were collected and weighed. The tumor tissue was checked by the immunohistochemical staining assay. Results:The CCK-8 and clone formation assay results showed that fentanyl reduced the antitumor effect of sorafenib in HCC. Fentanyl upregulated the expression of autophagy-related proteins Beclin-1 and LC3, and immunofluorescence and transmission electron microscopy showed that fentanyl could increase the levels of autophagy in HCC cells. DCFH-DA staining showed that fentanyl increased reactive oxygen species production, and Protein immunoblotting test result showed that fentanyl reduced the levels of phosphorylated protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR). The autophagy inhibitor 3-methyladenine (3-MA) could block the protective autophagy induced by fentanyl, and then reduce the adverse effects of fentanyl on sorafenib. There was no statistical difference in tumor volume at 4th, 8th and 12th day among three groups ( P>0.05); the tumor volume 16th, 20th and 24th and weight in fentanyl + sorafenib group and sorafenib group were significantly lower than those in control group: (275.00 ± 11.58) and (174.00 ± 91.42) mm 3 (307.40 ± 81.39) mm 3, (701.00 ± 105.08) and (563.60 ± 89.59) mm 3 vs. (855.20 ± 68.71) mm 3, (971.60 ± 79.87) and (691.80 ± 11.17) mm 3 vs. (1 177.20 ± 105.79) mm 3, (705.00 ± 35.50) and (540.20 ± 80.76) mg vs. (1 118.40 ± 76.81) mg, the indexes in sorafenib group were significantly lower than those in fentanyl + sorafenib group, and there were statistical differences ( P<0.05). The immunohistochemical staining assay result showed that Ki67 and LC3 positive cells (brown cells) in fentanyl + sorafenib group were significantly more than those in sorafenib group. Conclusions:Fentanyl reduces the suppressive effect of sorafenib on HCC tumor growth by inducing protective autophagy, which could be weakened by adding autophagy inhibitors.

Viral pneumonia （VP） is an inflammatory disease caused by one or more viruses that infect the upper respiratory tract and spread downward. Causing varying degrees of pulmonary parenchymal damage， VP poses a serious threat to the society and public health. The treatment of VP now faces the dilemma of drug shortage， since Western medicine can only alleviate symptoms and lacks specific treatment methods. In traditional Chinese medicine （TCM）， VP is assigned as an epidemic disease， with the etiology attributed to epidemic toxin and six excesses and the pathological factors of dampness， heat， toxin， deficiency， and stasis. The basic pathogenesis of VP is Yin-Yang imbalance， dysfunction of Zang-Fu organs， and healthy Qi deficiency. Accordingly， the treatment should follow the principle of replenishing healthy Qi and expelling pathogen. The treatment method of VP is mainly developed based on syndrome differentiation of six meridians， defense-Qi-nutrient-blood， and triple energizer. Xuanfei Baidu prescription （XFBD） is an effective prescription developed by Academician ZHANG Boli and Professor LIU Qingquan by literature research and selection of multi-component Chinese medicine. It is the product of modern research combined with TCM. XFBD is modified from Maxing Shigantang， Maxing Yigantang， Tingli Dazao Xiefeitang， Qianjin Weijingtang， and Buhuanjin Zhengqisan. It is mainly used to treat epidemic diseases with the syndrome of dampness toxin stagnating in the lung， with the effects of ventilating lung and resolving dampness， clearing heat and expelling pathogen， purging lung， and removing toxin， demonstrating the potential for the prevention and treatment of VP. This paper reviews the research progress of XFBD in combating VP in terms of the prescription composition， compatibility ideas， indications， and clinical new applications， as well as the pharmacological mechanisms of inhibiting virus， reducing inflammation， regulating immune system， ameliorating pulmonary fibrosis， and modulating intestinal flora. In addition， we put forward our thoughts and suggestions on the problems in the research， with a view to informing the clinical use of drugs and the basic research on the treatment of VP including COVID-19.

Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.

Objective: To under the prevalence of malnutrition and its associated factors in school aged children with cerebral palsy, so as to provide a basis for relevant departments to formulate targeted policies. Methods: From July to August 2023, the researchers selected 333 children with cerebral palsy and 960 children with other diseases aged 6-18 years who were residents of a social welfare institution in Guangzhou, China. Their height and weight were measured and a nutritional status analysis was carried out using a cluster sampling method. Multivariate Logistic analysis was performed to analyze the relative factors and malnutrition status of school aged children with cerebral palsy. Results: The prevalence of growth retardation among school aged children with cerebral palsy was 74.5%, with rates of stunting, normal nutrition status, and overweight/obesity being 17.7%, 7.2%, and 0.6%, respectively. The results of the univariate analysis revealed statistically significant differences in the detection rate of malnutrition among school aged children with cerebral palsy based on gender, gross motor function classification system (GMFCS) grading, and the presence of swallowing disorders ( χ 2=6.02, 15.23, 32.16, P <0.05). The results of the multivariate Logistic regression analysis showed that gender ( OR=0.37, 95%CI =0.15-0.91), dysphagia (OR=4.10, 95%CI =1.39-12.12), and GMFCS classification ( OR=1.45, 95%CI =1.04-3.01) were influencing factors of malnutrition ( P <0.05). Conclusions The detection rate of malnutrition among children and adolescents with cerebral palsy in welfare institutions was found to be relatively high, and influenced by various factors. Corresponding nutritional interventions should be developed and implemented based on the risk factors of malnutrition in school aged children with cerebral palsy to improve their nutritional status.

Objective We aimed to investigate(i)the preventive and therapeutic effects of Huogu Muli Prescription(HGMLP),a Chinese medical compound consisting of epimedii folium,drynariae rhizoma,and ostreae concha,on postmenopausal osteoporosis(PMOP)rats and(ii)whether it exerts its effects by regulating the osteoclast-osteogenesis balance.Methods Forty-eight female Sprague-Dawley rats were randomly divided into the following six groups:(i)the sham-operated group,(ii)the model group,(iii)the Qianggu Capsule group,(iv)the calcium carbonate group,and(v,vi)the HGMLP low-dose and high-dose groups(n = 8 rats per group).After adaptive feeding,rats in all groups except the sham-operated group were treated with bilateral ovarian castration to establish the PMOP model.Each day,rats in the Qianggu Capsule group received 0.054 g/kg Qianggu Capsule suspension intragastrically,rats in the calcium carbonate group received 1.670 g/kg calcium carbonate suspension intragastrically,and rats in the HGMLP low-dose and high-dose groups received 0.188 g/kg and 0.375 g/kg HGMLP intragastrically.Rats in the sham-operated group and the model group received an equal volume of normal saline intragastrically.After 90 consecutive days,serum estradiol(E2),estrogen receptor α(ERα),procollagen typeⅠN propeptide(PINP),and tartrate-resistant acid phosphatase 5b(TRACP-5b)were detected by ELISA.Total antioxidant capacity(T-AOC),superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels were measured by colorimetry.Bone mineral density(BMD),trabecular number(Tb.N),trabecular separation/spacing(Tb.Sp),trabecular thickness(Tb.Th),and structure model index(SMI)were measured by Micro-CT,and the microstructure of cancellous bone was observed.The expressions of osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK),RANK ligand(RANKL),phosphorylation of forkhead box O3(FoxO3α),Wnt2,β-catenin,and peroxisome proliferator-activated receptor γ(PPARγ)in rat femur tissue were detected by Western blotting.Results(i)The serum levels of E2 and ERα increased in the Qianggu Capsule group and HGMLP groups,compared with the model group(all P<0.05).(ii)Compared with the model group,the serum levels of PINP,TRACP-5b decreased and PINP/TRACP-5b increased in both the Qianggu Capsule group and HGMLP high-dose group(all P<0.05).(iii)The activities of T-AOC,AOD,and CAT in the Qianggu Capsule group and HGMLP groups were higher than those in the model group,while the content of MDA lower(all P<0.05).(iv)Compared with the model group,the femoral BMD,Tb.Th,and Tb.N increased in the Qianggu Capsule group and HGMLP groups,while the femoral Tb.Sp and SMI decreased(all P<0.05);the femoral BMD increased and the Tb.Sp decreased in the calcium carbonate group(all P<0.05).(v)The protein expressions of RANKL,RANK,FoxO3α,and PPARγ in the Qianggu Capsule group and HGMLP groups were lower than those in the model group,while the protein expressions of OPG,Wnt2,and β-catenin were higher(all P<0.05).Conclusion HGMLP can significantly increase estrogen levels,inhibit osteoclast differentiation,and inhibit bone resorption in the PMOP rats.It also alleviates oxidative stress,promotes osteogenic differentiation,inhibits lipogenic differentiation,improves bone formation,and recovers the balance between osteoclasts and osteoblasts,thus achieving prevention and treatment of PMOP.The potential mechanism of HGMLP may be related to regulation via the OPG/RANKL/RANK or FoxO3α/Wnt2/β-catenin/PPARγ pathways.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.