BACKGROUND:Naringin has been shown to promote the proliferation and osteogenic differentiation of bone marrow derived mesenchymal stem cells,making it a potential candidate for treating osteoporosis andenhancing fracture healing.However,its clinical application is limited by its low bioavailability.OBJECTIVE:To prepare chitosan/β-tricalcium phosphate scaffolds loaded with naringin and characterize their biological properties.METHODS:Chitosan/β-tricalcium phosphate scaffolds were prepared by freeze-drying and chemical crosslinking.The chitosan/β-tricalcium phosphate scaffolds were immersed in anhydrous ethanol solution containing naringin for 3 hours.After vacuum cold drying,chitosan/β-tricalcium phosphate/naringin scaffolds were obtained.The pore size,porosity,swelling rate,degradation rate,mechanical properties,and in vitro release capacity of naringin of the scaffolds were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of chitosan/β-tricalcium phosphate scaffolds and chitosan/β-tricalcium phosphate/naringin scaffolds,respectively,and cell proliferation,adhesion,activity and alkaline phosphatase activity after osteogenic differentiation were detected.RESULTS AND CONCLUSION:(1)The results of scanning electron microscopy showed that the naringin-chitosan/β-tricalcium phosphate composite scaffold had a porous mesh structure.The average pore diameter was(106.82±25.22)μm;the porosity was(76.26±4.81)％;24-hour swelling rate was(796.17±31.76)％;in vitro degradation rate of 7.71％at 4 weeks,and naringin could be slowly released in vitro for 9 days.There was no significant difference in the average pore size,porosity,24-hour swelling rate,in vitro degradation rate,compression strength and compression modulus at 4 weeks between the chitosan/β-tricalcium phosphate scaffold and the chitosan/β-tricalcium phosphate scaffold(P＞0.05).(2)Rat bone marrow mesenchymal stem cells adhered well to the surfaces of the two scaffolds and had good activity.Compared with the chitosan/β-tricalcium phosphate scaffold,the chitosan/β-tricalcium phosphate/naringin scaffold promoted the proliferation of rat bone marrow mesenchymal stem cells(P＜0.05),and increased the alkaline phosphatase activity of bone marrow mesenchymal stem cells after osteogenic differentiation(P＜0.05).(3)The results show that the chitosan/β-tricalcium phosphate/naringin scaffolds exhibit favorable physical properties and can effectively promote the adhesion,proliferation,and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.

BACKGROUND:Naringin has been shown to promote the proliferation and osteogenic differentiation of bone marrow derived mesenchymal stem cells,making it a potential candidate for treating osteoporosis andenhancing fracture healing.However,its clinical application is limited by its low bioavailability.OBJECTIVE:To prepare chitosan/β-tricalcium phosphate scaffolds loaded with naringin and characterize their biological properties.METHODS:Chitosan/β-tricalcium phosphate scaffolds were prepared by freeze-drying and chemical crosslinking.The chitosan/β-tricalcium phosphate scaffolds were immersed in anhydrous ethanol solution containing naringin for 3 hours.After vacuum cold drying,chitosan/β-tricalcium phosphate/naringin scaffolds were obtained.The pore size,porosity,swelling rate,degradation rate,mechanical properties,and in vitro release capacity of naringin of the scaffolds were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of chitosan/β-tricalcium phosphate scaffolds and chitosan/β-tricalcium phosphate/naringin scaffolds,respectively,and cell proliferation,adhesion,activity and alkaline phosphatase activity after osteogenic differentiation were detected.RESULTS AND CONCLUSION:(1)The results of scanning electron microscopy showed that the naringin-chitosan/β-tricalcium phosphate composite scaffold had a porous mesh structure.The average pore diameter was(106.82±25.22)μm;the porosity was(76.26±4.81)％;24-hour swelling rate was(796.17±31.76)％;in vitro degradation rate of 7.71％at 4 weeks,and naringin could be slowly released in vitro for 9 days.There was no significant difference in the average pore size,porosity,24-hour swelling rate,in vitro degradation rate,compression strength and compression modulus at 4 weeks between the chitosan/β-tricalcium phosphate scaffold and the chitosan/β-tricalcium phosphate scaffold(P＞0.05).(2)Rat bone marrow mesenchymal stem cells adhered well to the surfaces of the two scaffolds and had good activity.Compared with the chitosan/β-tricalcium phosphate scaffold,the chitosan/β-tricalcium phosphate/naringin scaffold promoted the proliferation of rat bone marrow mesenchymal stem cells(P＜0.05),and increased the alkaline phosphatase activity of bone marrow mesenchymal stem cells after osteogenic differentiation(P＜0.05).(3)The results show that the chitosan/β-tricalcium phosphate/naringin scaffolds exhibit favorable physical properties and can effectively promote the adhesion,proliferation,and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.

ObjectiveTo investigate the effect of Qingrun prescription（QRP）-containing serum on improving insulin resistance in HepG2 cells and its potential mechanisms. MethodsAn insulin resistance model was established in HepG2 cells with 1×10^-6 mol·L^-1 insulin. Branched-chain α-keto acid dehydrogenase （BCKDH） gene silencing was achieved using siRNA， and the cells were divided into 8 groups： normal group， model group （1×10^-6 mol·L^-1 insulin）， metformin group （1 mmol·L^-1 metformin）， high-， medium-， and low-dose QRP groups （20%， 10%， and 5% QRP-containing serum， respectively）， QRP + siRNA-silenced BCKDH （si-BCKDH） group （10% QRP-containing serum + si-BCKDH）， and QRP + si-NC group （10% QRP-containing serum + si-NC）. Glucose levels in the supernatant were measured with a glucose assay kit， while glycogen content was assessed using a glycogen assay kit. Levels of branched-chain amino acids （BCAAs） and branched-chain keto acids （BCKAs） were determined using ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS）. mRNA transcription and protein expression levels of BCKDH， dishevelled， Egl-10， and pleckstrin （DEP） domain-containing mammalian target of rapamycin （mTOR）-interacting protein （DEPTOR）， mTOR， and ribosomal protein S6 kinase 1 （S6K1） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared to the normal group， the model group exhibited significantly decreased glucose consumption and glycogen content， increased levels of BCAAs and BCKAs， downregulated expression of BCKDH and DEPTOR， and upregulated mTOR and S6K1 expression （P<0.01）. In comparison to the model group， QRP treatment at all doses significantly enhanced glucose consumption and glycogen content while reducing BCAAs and BCKAs levels （P<0.01）. The high- and medium-dose QRP groups demonstrated significant upregulation of BCKDH mRNA transcription and protein expression， as well as DEPTOR mRNA transcription. Moreover， the DEPTOR protein expression level was significantly increased in high-， medium-， and low-dose QRP groups， while mTOR and S6K1 mRNA and protein expression levels were markedly downregulated （P<0.05， P<0.01）. Compared to the QRP + si-NC group， the QRP + si-BCKDH group exhibited increased BCAAs and BCKAs levels， significantly decreased BCKDH mRNA transcription and protein expression， downregulated DEPTOR mRNA and protein expression， and upregulated mTOR and S6K1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionQRP may improve insulin resistance by reprogramming BCAAs metabolism. This effect involves upregulating BCKDH， reducing BCAAs and BCKAs levels， and suppressing the mTOR pathway activation.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Objective: To investigate the status of salt-restriction spoons use among residents in Zhejiang Province, so as to provide evidence for optimizing salt-reduction intervention strategies and preventing chronic disease. Methods: Residents aged 18-69 from five counties (cities/districts) in Zhejiang Province were selected using a multi-stage stratified random sampling method. Demographic characteristics, dietary habits, and salt-restriction spoons use were collected using questionnaires. The rate of salt-restriction spoons use and correct rate of salt-restriction spoons use were analyzed. Factors affecting salt-restriction spoons use among residents were analyzed by multivariable logistic regression model. Results: Totally 7 601 questionnaires were allocated, and 7 509 valid questionnaires were recovered, with an effective recovery rate of 98.79%. The respondents included 3 744 males (49.86%) and 3 765 females (50.14%). The mean age was (44.81±14.03) years. The rate of salt-restriction spoons use was 11.97%, the correct rate of salt-restriction spoon use was 52.73%. Multivariable logistic regression analysis showed that rural (OR=0.851, 95%CI: 0.731-0.991), education level of primary school and below (illiterate or semi-literate, OR=0.269, 95%CI: 0.172-0.420; primary school, OR=0.595, 95%CI: 0.436-0.811), and excessive dietary salt intake (OR=0.718, 95%CI: 0.559-0.922) were inhibiting factors for salt-restriction spoons use among residents; physical exercise (OR=1.581, 95%CI: 1.362-1.836) and received health education on a low-salt diet (OR=2.082, 95%CI: 1.790-2.421) were promoting factors for salt-restriction spoons use among residents. Conclusions The rate of salt-restriction spoons use among residents in Zhejiang Province was relatively low, primarily influenced by region, educational level, physical activity, dietary salt intake, and health education on a low-salt diet. It is recommended that propose a multi-component intervention strategy centered on skill enhancement and health education, delivered through progressive staged implementation, to promote sustained adoption of salt-restriction spoons among residents.

Objective To verify the safety and effectiveness of a new percutaneous controllable curved plasma radiofrequency instrument for nucleus pulposus ablation. Methods A new percutaneous controllable curved plasma radiofrequency instrument were designed (controllable curved group), and its ablation effect was compared with the currently used straight head non-bendable plasma ablation instrument (non-bendable group) on gross specimens. The ablation instrument was placed through the right intervertebral foramen, and continuous ablation on the same intervertebral disc was conducted for three times. The ablation range and trajectory were recorded, and the temperature changes in the front, back, left, and right of the ablation center during and 15 seconds after ablation were monitored by the inserted temperature probe. Results There were no difference in temperature changes in the front, back, right regions of the ablation center during and 15 seconds after ablation between the two groups. The temperature changes in the left region of the ablation center both during and 15 seconds after 3rd ablation were larger than those in the non-bendable group (P＜0.01). Compared with the non-bendable group, the controllable curved group achieved angle control and larger single ablation area (2.282 5 mm² vs 1.135 8 mm², P＜0.000 1). Conclusions This new percutaneous controllable curved plasma ablation instrument can achieve angle control and ablation on the side opposite to the puncture site, increase ablation volume, and is safe.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People