Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Purpose/Significance The data security management system is built based on the big data of medical alliance to achieve the purpose of enhancing data protection,reducing security risks and improving data security.Method/Process By analyzing the busi-ness scenario of medical alliance,data security policies and application security technologies are established in the full life cycle of collec-tion,transmission,storage,processing,sharing and destruction,and the construction of data security system is improved.Result/Con-clusion The data security management system is a"safety belt"for the business of medical alliance.With a clear security system and standards as the outline,it provides an effective path for the legal and compliant development of hospital business and establishes a feed-back mechanism.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Objective To explore the current status of clinical inertia in the treatment of patients with type 2 diabetes mellitus (T2DM) in the suburbs of Shanghai and analyze its risk factors. Methods A total of 1, 804 T2DM patients who visited the Endocrinology and Metabolism Clinic of Shanghai Sixth People's Hospital from November 2022 to November 2023 were selected as research objects. Patients were divided into clinical inertia group and non-clinical inertia group based on whether clinical inertia occurred during their treatment, and demographic and clinical data were collected. Logistic regression analysis was used to identify risk factors for clinical inertia in the treatment of T2DM patients. Results The incidence of clinical inertia in T2DM patients was 52.00% (938/1, 804). The results of multivariate Logistic regression analysis showed that longer diabetes duration, high level of glycated hemoglobin (HbA1c), high score of the Problem Areas in Diabetes Scale(PAID) score, taking over two oral medications, shorter life expectancy, and coexisting retinopathy were risk factors for clinical inertia in the treatment of T2DM patients (P < 0.05). Conclusion The incidence of clinical inertia is high in T2DM patients during treatment in the suburbs of Shanghai. T2DM patients with poor glycemic control, longer disease duration, high level of psychological distress, taking over two oral medications, shorter life expectancy, and coexisting retinopathy are more prone to occur clinical inertia.

Objective:To explore the safety and efficacy of radiofrequency in the treatment of overactive bladder(OAB).Methods:A prospective, multicenter, non-randomized controlled trial was conducted. Eligible patients were divided into test group and control group in Zhejiang Provincial People’Hospital, The First Affiliated Hospital of Wenzhou Medical University, and Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from March 2019 to June 2020. Inclusion criteria: patients diagnosed with OAB, and bladder capacity>100ml. Exclusion criteria: pregnant and lactating women; patients with secondary OAB symptoms such as urinary tract obstruction; patients with uncontrolled urinary tract infection within 1 week; patients in stable stage by using other treatment methods; patients implanted with any nerve stimulator, cardiac pacemaker or implantable defibrillator; patients with malignant tumors, serious cardiovascular, cerebrovascular diseases, renal insufficiency or received BTX treatment in recent 12 months. The patients were allocated to test group and the control group in a ratio of 2∶1 according to the time sequence of the visit. The patients in the test group were treated with radiofrequency treatment. After entering the group, they were treated for 4 times at the 1st, 2nd, 7th and 8th week respectively. In the control group, the energy was turned off during the radiofrequency treatment. The patients were followed-up every week until the end of the 12th week. The treatment success rate [the average frequency of urination in 24 h was reduced more than 50% from the baseline or returned to the normal (≤8 times/day) or the average frequency of urgent urination in 24 h was reduced more than 50% from the baseline], the frequency of urination, urgent urination and nocturnal urination before and after treatment, the residual urine volume of the bladder, the quality of life (QOL) score and the occurrence of catheter related adverse events in two groups were compared.Results:114 patients were enrolled in the study, including 76 patients in the test group and 38 patients in the control group. There were no significant differences in the age [(44.2±12.8) vs. (41.7 ± 12.1) years old], male female ratio (13/63 vs. 4/34), average course of disease [2.0(1.2, 5.0) vs. 2.0 (1.0, 4.0) years], the frequency of urination[12.8 (10.6, 16.8) vs. 12.8 (10.3, 17.0) times], urgency urination [11.8(9.3, 15.8) vs. 11.8 (9.0, 17.0) times], nocturia [2.7 (1.3, 3.7) vs. 2.3(0.7, 3.3) times], residual urine volume of bladder [12.0 (3.0, 28.0) vs. 14.0 (3.7, 20.0) ml ] and the QOL score [5.0(4.0, 5.0) vs. 4.0(4.0, 5.0)]before the treatment between the two groups ( P>0.05). The treatment success rate in the test group was 76.3% (58/76), while 26.3% (10/38) in the control group, with a statistically significant difference ( P<0.01). There were significant differences between the test group and control group in the frequency of urination [9.7 (7.7, 12.0) vs. 12.9 (9.6, 15.7) times], urgent urination [7.3 (5.0, 10.0) vs. 11.7 (7.3, 15.3) times], nocturia [1.3 (0.7, 2.0) vs. 1.7 (1.0, 3.0) times] and the QOL score of the patients[3.0(1.0, 3.0) vs. 4.0(3.0, 4.5)]after the treatment(all P<0.05). The frequency of urination, urgency urination, nocturia, the residual urine volume and the QOL score in the test group were significantly improved ( P<0.05) after the treatment.The frequency of urination, nocturia, residual urine volume and the QOL score in the control group were improved ( P<0.05) after the treatment. 13 (11.4%) patients had catheter related adverse events. In the test group and the control group, there were 7 cases of macroscopic hemorrhage caused by the placement of instruments (5/76 vs. 2/38), 5 cases of acute urinary tract infection within 3 days (3/76 vs. 2/38), and 1 case of instrument breakage (catheter breakage) (0/76 vs. 1/38). There were no significant differences in the adverse events between the two groups ( P> 0.05). Conclusions:Radiofrequency treatment of OAB can effectively improve the symptoms of patients, improve the QOL of patients, and has low incidence of adverse events, with good efficacy and safety.

Objective:To investigate the surgical efficacy of split liver transplantation.Methods:Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group ( n=60) and whole liver transplantation group ( n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m 2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m 2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results:Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time( M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours, U=6.608, P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours, U=2.825, P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes, U=1.048, P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml, U=0.966, P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U, U=1.732, P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days, U=2.677, P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days, U=2.237, P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51), χ2=3.935, P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days, U=1.607, P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group( P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively( P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion:Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

Objective:To investigate the surgical efficacy of split liver transplantation.Methods:Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group ( n=60) and whole liver transplantation group ( n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m 2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m 2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results:Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time( M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours, U=6.608, P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours, U=2.825, P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes, U=1.048, P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml, U=0.966, P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U, U=1.732, P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days, U=2.677, P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days, U=2.237, P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51), χ2=3.935, P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days, U=1.607, P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group( P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively( P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion:Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification.

OBJECTIVE To investigate the mechanism of glucose -6-phosphate dehydrogenase （G6PD）-induced sorafenib - resistance in hepatocarcinoma cell based on phoshorylated 3-kinase/protein kinase B （PI3K/Akt）signaling pathway . METHODS Cell lines including hepatocarcinoma cell Huh 7，sorafenib-resistant cell Huh 7-SR，G6PD overexpressed cell Huh 7-G6PD and its control cell Huh 7-CT，and compounds including G 6PD inhibitor （6-Aminonicotinamide，6AN）and sorafenib were used as objects or intervention drugs in these research . CCK8 assay was applied to evaluate cell viability . The protein levels of G 6PD and the phosphorylation levels of PI 3K/Akt signaling pathway were detected by Western blot . Flow cytometry was utilized to investigate cell apoptosis. RESULTS Compared with Huh 7 cells，the protein level of G 6PD was significantly increased in Huh 7-SR cells （P＜ 0.05）. The combination of 6AN and sorafenib reduced cell viability of Huh 7-SR cells （P＜0.01）. However，compared with Huh 7- CT，increased cell viability and decreased cell apoptosis rate were observed in Huh 7-G6PD cells while cells were treated with sorafenib（P＜0.01）. Mechanistically，the phosphorylation levels of PI 3K and Akt were significantly decreased in Huh 7-SR cells that were treated with 6AN（P＜0.05）. Moreover，under the condition of no drug intervention ，the phosphorylation levels of PI 3K and Akt were significantly elevated in Huh 7-G6PD cells when compared with Huh 7-CT（P＜0.01）. CONCLUSION G6PD could induce sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway .