This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To explore the effects of different glucose concentrations on the synthesis and secretion of bone collagen in osteoblasts and the impact of diabetes on bone quality in mice.Methods(1)Primary osteoblasts were extracted from the skulls of neonatal mice via collagenase digestion and cultured in four groups under different glucose concentrations:normal glucose(5.5 mmol/L),moderate glucose(11.5 mmol/L),moderate-high glucose(16.5 mmol/L),and high glucose(25 mmol/L).EdU staining was performed to evaluate cell proliferation,while the Transwell assay was used to assess cell migration.Immunofluorescence and Western blotting were performed to detect and quantitatively analyze the content of type Ⅰ collagen(Col-1).Alizarin red S(ARS)staining and alkaline phosphatase(ALP)staining were applied to assess the effects of different glucose concentrations on osteogenic differentiation.(2)Six-week-old male C57BL/6 mice were randomly divided into control group and model group(5 in each group).The model group was fed a high-fat diet for 4 weeks followed by streptozotocin(STZ)injection to establish a diabetic mouse model.The osteogenic differentiation capacity of primary osteoblasts from both groups was assessed.(3)Micro-computed tomography(Micro-CT)was employed to analyze femoral bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular number(Tb.N),and trabecular separation(Tb.Sp).Three-point bending test was conducted to evaluate mechanical parameters including maximum load,Young's modulus,fracture energy,and stiffness.RT-qPCR was employed to assess the expression of osteogenic differentiation genes(Alp,Opn,Col1a1,and Lox).Masson staining and Mallory staining were used to evaluate Col-1 content in trabecular bone.Results(1)EdU and Transwell assay results demonstrated that with the gradual increase in glucose concentration,the proliferation and migration abilities of osteoblasts were significantly decreased(P<0.001),and the protein expression levels of Col-1 and lysyl oxidase(LOX)were significantly reduced(P<0.01 or P<0.001).ARS and ALP staining revealed that calcium salt deposition and ALP activity in osteoblasts were significantly decreased with increasing glucose concentration(P<0.05 or P<0.001).(2)Compared with control group,mice in model group exhibited typical"three polies and one weight loss"symptoms(polyuria,polydipsia,polyphagia,and weight loss)of diabetes,and ARS and ALP staining showed a significant reduction in osteoblasts(P<0.001).(3)Micro-CT and three-point bending test results indicated that,compared with control group,mice in model group showed microarchitectural deterioration of bone,decreased Tb.N,increased Tb.Sp,and significantly reduced maximum load,Young's modulus,fracture energy,and stiffness(P<0.05).RT-qPCR results showed that the relative mRNA expression levels of osteogenic differentiation genes(Alp,Opn,Col1a1,and Lox)were significantly decreased in model group compared with control group(P<0.01 or P<0.001).Masson and Mallory staining indicated a significant reduction in collagen content in model group compared with control group(P<0.01).Conclusions High-glucose environment inhibits osteoblast proliferation,differentiation,and migration.Diabetic mice exhibit reduced bone quality and increased bone fragility,potentially mediated by decreased lysyl oxidase and collagen levels.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.

Objective To investigate the effect of enhanced three-dimensional variable reversal angle fast spin-echo single breath-hold magnetic resonance cholangiopancreatography(3D SPACE BH MRCP)with high parallel acquisition factor on image quality.Methods A total of 33 patients with clinically suspected pancreatobiliary duct disease who underwent epigastric enhancement and magnetic resonance cholangiopancreatography(MRCP)examination were prospectively collected.All patients were required to acquire a single 3D SPACE BH MRCP before and after enhancement.The signal intensity of the common bile duct and background,signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and subjective scores of 3D SPACE BH MRCP before and after enhancement were recor-ded.Statistical analyses were performed using the Wilcoxon signed-rank sum test,and the Kappa test was used to assess the consis-tency of scores between the two readers.Results The difference in the common bile duct signals of 3D SPACE BH MRCP before and after enhancement was not statistically significant(Z=-1.215,P=0.224),however the background signal was decreased after enhancement with a significant difference(Z=-3.878,P＜0.001).The SNR and CNR of the images were better than those of 3D SPACE BH MRCP before enhancement(Z=-4.458,P＜0.001;Z=-4.583,P＜0.001).The subjective score of 3D SPACE BH MRCP after enhancement was better than that before enhancement,and the difference was statistically significant(Z=-2.646,P=0.008).There was a strong inter-reader agreement before and after enhancement 3D SPACE BH MRCP scores(Kappa=0.70,P＜0.01 and Kappa=0.73,P＜0.01).Conclusion The enhanced 3D SPACE BH MRCP between portal vein phase and equilibrium phase dose not affect the display of pancreaticobiliary duct,and can effectively suppress the background signal and improve the image quality of MRCP.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023.Methods:ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed.Results:From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) ( P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion:SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023.Methods:ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed.Results:From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) ( P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion:SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

BACKGROUND: Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. METHODS: An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity. RESULTS: The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats. CONCLUSIONS SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*