OBJECTIVE: To investigate the hepatotoxicity of alkaloids from Euodiae Fructus combined with berberine (BBR) in Zuojin Pill, and to preliminarily explore the possible detoxification mechanism of the combination components. METHODS: The combination ratio of components was determined by the maximum concentration (Cmax) of the chemical components in Zuojin Pill. HepG2 cell model was used to investigate the combined toxicity of the hepatotoxic components from Euodiae Fructus, such as evodiamine (EVO) or dehydroevodiamine (DHED), with BBR for 48 h. The experimental groups were set as follows: the vehicle control group, the EVO group, the DHED group, the BBR group, and the combination group of EVO or DHED with BBR. The cell counting kit-8 (CCK-8) method was used to determine the cell viability, and the combination index (CI) was used to determine the combined toxicity of the components. The alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydroge-nase (LDH), and alkaline phosphatase (ALP) activities as well as total bilirubin (TBIL) content in the cell culture supernatant were detected. The protein expression levels of bile acid transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), were detected by Western blot. The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in HepG2 cells were detected. RESULTS: Compared with EVO or DHED group, the combination of EVO 1 μmol/L with BBR 10 μmol/L or DHED 50 μmol/L with BBR 35 μmol/L significantly increased cell viability of HepG2 cells (P < 0.01), with CI values of 77.89 or 4.49, respectively, much greater than 1. Significant decreases in the activities of ALT, AST, LDH, ALP, and TBIL content in the cell culture supernatant were found in both combination groups (P < 0.05, P < 0.01). Compared with the EVO group, the combination of EVO with BBR upregulated the protein expression levels of BSEP and MRP2. Compared with the DHED group, the combination of DHED with BBR significantly downregulated the protein expression levels of BSEP and MRP2 (P < 0.01). Compared with EVO or DHED group, the combination of EVO or DHED with BBR significantly reduced the MDA content in HepG2 cells (P < 0.05, P < 0.01). CONCLUSION A certain ratio of BBR combined with EVO or DHED had an antagonistic effect on HepG2 cytotoxicity, which might be related to regulating the expression of bile acid transpor-ters, and reducing lipid peroxidation damage.
Humans ; Hep G2 Cells ; Berberine/pharmacology* ; Drugs, Chinese Herbal/toxicity* ; Evodia/chemistry* ; Alkaloids/pharmacology* ; Cell Survival/drug effects* ; Multidrug Resistance-Associated Proteins/metabolism* ; Multidrug Resistance-Associated Protein 2 ; Quinazolines

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

With the rapid changes in people's lifestyles, natural and social environments in recent years, the prevalence of chronic and non-communicable diseases in China and its related risk factors have also had tremendous changes. The epidemiological characteristics of chronic and non-communicable diseases and their risk factors vary throughout the country, and the impact of unique climate, diet and lifestyle in southern China on the incidence and prevalence of chronic and non-communicable chronic diseases remains to be elucidated. Therefore, large-scale cohort study is urgently needed to provide evidence for the etiological research and management of chronic and non-communicable chronic diseases in different areas, and for the national management strategy for major chronic and non-communicable diseases. The prospective cohort study of chronic and non-communicable diseases in general population in southern China was established in December 2017. The study recruited permanent residents aged 35-74 years from both urban and rural areas in Guangdong, Hainan, Fujian Provinces and Guangxi Zhuang Autonomous Region. A big data platform of precision medicine which integrates health information with biological samples for long-term follow up has been established. A baseline database of 116 520 people aged (54.9±12.5) years, including 71 077 women (61.0%), has been established. Collecting questionnaire survey data, physical examination data, and biological samples. This paper briefly introduces the concept, design and progress of the prospective cohort study of chronic and non-communicable diseases in general population in southern China.

With the continuous advancement of health informatization and the wide application of medical big data, electronic health records came into being and spread rapidly. However, because electronic health records contain a large amount of private information, privacy protection is the primary consideration for the sustainable development of electronic health records. By analyzing the shortcomings of privacy protection of electronic health records in law, technology, management and protection consciousness, this paper put forward some countermeasures, such as perfecting the relevant laws and regulations of privacy protection of electronic health records, improving the technical level, improving the management defects of electronic health records, and cultivating the privacy protection consciousness of professionals and the public, so as to improve the overall privacy protection level of China’s health records information management system and provide effective protection for the privacy information of Chinese residents’ electronic health records.

Objective To explore the clinical value of 3D fast spin echo with an extended echo train acquistion (CUBE) T1WI enhancement sequence for purulent meningitis by comparing to contrast?enhanced T2WI?FLAIR sequence in the detection of lesions. Methods From August 2016 to July 2017, children with clinically suspected purulent meningitis underwent cranial magnetic resonance examination in our hospital. There were 35 children, 19 males and 16 females, aged 2 months to 3 years (median age 8 months) in total.A GE Discovery MR 750 3.0 T scanner was used to perform routine plain and enhanced scan in all children. After enhancement, the sequences of CUBE T1WI and FLAIR T2WI were applied randomly. Using the FLAIR T2WI enhancement sequence as the reference, we evaluated the detection rate of CUBE T1WI enhancement sequence for dura mater and leptomeningeal thickening. The number of enhanced lesions detected was tested by χ2 test. Results The enhanced FLAIR T2WI sequence showed 21 cases with dural enhancement, showing a rate of 60.0%. The enhanced CUBE T1WI sequence showed 31cases with dural enhancement, showing a rate of 88.6%. There were significant differences between the dural lesions detected(χ2＝6.058, P<0.01). The enhanced FLAIR T2WI sequence showed 16 cases of leptomeningeal enhancement,showing a rate of 45.7%. The enhanced CUBE T1WI sequence showed 19 cases of leptomeningeal enhancement,showing a rate of 54.3%.The enhanced CUBE T1WI sequence was not significantly higher than that of enhanced T2WI?FLAIR sequence in displaying leptomeningeal enhancement (χ2=0.229, P>0.05). Conclusion Enhancement of the CUBE T1WI sequence enables better visualization of meningeal thickening than FLAIR T2WI. It has great clinical value in the diagnosis of purulent meningitis in children.

Objective To study the regulatory effect of interleukin-17 on the production of inflammation and bone erosion related factors of fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) patients and to investigate whether signal transducer and activator of transcription 3 (STAT3) is implicated in this regulatory effect.Methods FLSs were acquired through primary culture from RA patients.Receptor activator for nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression in FLSs were determined using western blot analysis.The level of IL-6,granulocyte-mac rop hage colony stimulating fac tor (GM-CSF)and IL-8 were determined by enzyme linked immunosorbent assay (ELISA) assay.Statistical product and service solutions (SPSS) 17.0 statistical software was used for single factor analysis of variance and LSD-t comparison between each two groups.Results IL-17 stimulated FLSs and promoted the release of IL-6,GM-CSF and IL-8 (t=2.135,P＜0.01) and increased the production of RANKL (t=2.105,P＜0.01) and reduced the production of OPG (t=2.502,P＜0.01).However,targeted silencing of STAT3 could inhibit the effect of IL-17 on FLSs [control group:IL-6 (512±18) pg/ml;GM-CSF (591±25) pg/ml;IL-8 (473±10) pg/ml;RANKL (2.310±0.096);OPG (0.614±0.311);IL-17 group:IL-6 (1 630±39) pg/ml;GM-CSF (1 825±18) pg/ml;IL-8 (2 804±41) pg/ml;RANKL (4.010±0.256);OPG (0.131±0.101);STAT3 silent group:IL-6 (405±21) pg/ml;GM-CSF (451±12) pg/ml;IL-8 (370±9) pg/ml;RANKL (0.850±0.298);OPG (1.120±0.342)].Conclusion STAT3 pathway is critical to IL-17-induced regulatory effect on the release of inflammation and bone erosion related factors of FLSs.IL-17 can induce the inflammation and bone erosion of RA via STAT3.

Objective To evaluate the effects of intra-aortic balloon counterpulsation (IABP) on mortality of patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI).Methods Randomized controlled trials (RCTs) of IABP compared with non-IABP control in AMI patients, from January 1970 to May 2015, were searched from MEDLINE, Embase and Web of Science.The data were analyzed with software RevMan 5.0.Results Five RCTs involving 1 450 AMI patients, including 722 treated with IABP (IABP group) and 728 without IABP (non-IABP group), were included for analysis.Compared with non-IABP group, IABP did not significantly decrease the hospital mortality or 30-day mortality (OR=0.92, 95%CI: 0.69-1.25,P=0.61).According to the timing of IABP before or after PCI, it was further divided into IABP-before-PCI subgroup and IABP-after-PCI subgroup.Compared with non-IABP group, the 30-day mortality was not decreased in IABP-before-PCI subgroup or in IABP-after-PCI subgroup (OR=0.64, 95%CI: 0.23-1.78,P=0.39;OR=1.25, 95%CI: 0.42-3.77,P=0.69, respectively).According to complicating with cardiogenic shock (CS) or not, patients were divided to AMI with CS subgroup and AMI with no-CS subgroup;the hospital or 30-day mortality were not significantly decreased in both subgroups (OR=0.96, 95%CI: 0.70-1.32,P=0.80;OR=0.68, 95%CI: 0.28-1.70,P=0.27, respectively).Conclusion IABP does not decrease the 30-day mortality of AMI patients treated with PCI.

Ebola virus (EBOV) harbors an RNA genome encapsidated by nucleoprotein (NP) along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451-739) alone is capable of forming a helical nucleocapsid-like complex (NLC). However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451-739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro.
Ebolavirus ; chemistry ; genetics ; metabolism ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Nucleocapsid ; chemistry ; genetics ; metabolism ; RNA, Viral ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Virus Assembly