Objective:To establish the haemodynamic response during the verbal fluency task(VFT)in patients with MCI and to find a screening tool that could be used as a predictor of dementia. Method:Functional near-infrared spectroscopy(fNIRS)can detect changes in blood oxygen in the brain,thus revealing the patient's functional brain activity status,and is used to study the level of brain function in MCI.We evaluated the hemodynamic response in the prefrontal and temporal regions of MCI patients and healthy controls in our study. Result:The results found a significantly reduced haemodynamic response in the prefrontal brain regions in the MCI group. Conclusion:The results suggested that a reduced haemodynamic response in the prefrontal brain regions could be used as a diagnostic biomarker for dementia.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective:To evaluate the relationship between microRNA-27a (miR-27a) and silent information regulator 1 (SIRT1) during myocardial ischemia-reperfusion (I/R) in rats.Methods:Fifty clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 5 groups ( n=10 each) by the random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), AAV9-miR-27a overexpression + myocardial I/R group (AAV+ I/R group), miR-27a antagomir + myocardial I/R group (AG+ I/R group) and AAV9-miR-27a negative control+ myocardial I/R group (NC+ I/R group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion. At day 14 before ischemia, AAV9-miRNA-27a adeno-associated virus 2×10 11 v. g was injected via the tail vein in AAV+ I/R group, and AAV9-miR-27a NC 2×10 11 v. g was injected via the tail vein in NC+ I/R group. miR-27a antagomir 10 mg/kg was injected via the tail vein once a day at 3 days before ischemia in AG+ I/R group. At the end of 120 min of reperfusion, serum cardiac troponin T(cTnT), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH) concentrations and contents of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissues were determined by enzyme-linked immunosorbent assay, the percentage of myocardial infarct volume by TTC staining, the expression of miR-27a in myocardial tissues by quantitative real-time polymerase chain reaction, and the expression of SIRT1 in myocardial tissues by Western blot. Results:Compared with Sham group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in AAV+ I/R, and the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05), and no significant change was found in the parameters mentioned above in NC+ I/R group ( P>0.05). Compared with AAV+ I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05). Conclusions:miR-27a is involved in the pathophysiological mechanism underlying myocardial I/R injury probably through inhibition of SIRT1 expression in rats.

In the context of the digital economy， the operational relationship between traditional Chinese medicine （TCM） and Internet healthcare organizations as well as related governance institutions has attracted much attention. As the market scale of the Internet healthcare has continued to grow in recent years， the quality of Internet TCM healthcare has also been improved. By analyzing the development status of Internet TCM healthcare， it is proposed that Internet TCM health service should seize the opportunities and challenges in future， promote the growth of market scale from varied aspects， enhance patient-centered care awareness， and strengthen the promotion and popularization of digital services， thereby promoting the high-quality development of Internet TCM health service in the context of the digital economy.

Objective: To investigate the effect of silencing human leukocyte⁃associated antigen⁃G ( HLA⁃G) expression in the chorionic trophoblast cell line JEG⁃3 cells under hypoxic conditions on the biological function of JEG⁃3 cells and through the hypoxia response pathway of endothelial PAS1 region protein 1 (EPAS1)is involved in the molecular mechanism of preeclampsia under high altitude hypoxia. Methods: The expression of HLA⁃G in JEG⁃3 cells was inhibited by transfection of small interfering RNA (siRNA) . The JEG⁃3 cells after transfection were divided into four groups : normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group. CCK⁃8 test and Transwell test were used to detect the proliferation and invasion ability of the cells in four groups ; The effects of four groups of apoptosis and cell cycle were detected by flow cytometry; HLA⁃G and EPAS1 mRNA and protein expression levels were detected by real⁃time fluorescence quantitative PCR ( qPCR) and Western blot. Results : ① Compared with the normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group could reduce the proliferation activity and invasion ability of JEG⁃3 cells , and significantly increase the apoptosis rate. The hypoxic control group and hypoxic inhibition group also produced anobvious necrotic cell population ; Under the condition of hypoxia , after reducing the expression of HLA⁃G , the cell necrosis rate was further aggravated ; Whether under normoxia or hypoxia , inhibition of HLA⁃G expression caused the cells to be blocked in the G1 phase. ② Compared with the normoxic control group , hypoxia control group , normoxic inhibition group , and hypoxia inhibition group decreased the expression of HLA⁃G protein , and hypoxia and inhibition of HLA⁃G had a synergistic effect; Hypoxia⁃inducible factors⁃2α ( HIF⁃2α ) , vascular endothelial growth factor(VEGF) and endothelin⁃1(ET⁃1) protein expression could be added , inhibition of HLA⁃G decreased the expression of inducible nitric oxide synthase( NOS2) . Conclusion In the hypoxic environment , silencing HLA⁃G may affect the biological behavior of trophoblast through the EPAS1 hypoxic response pathway and participate in the occurrence and development of preeclampsia.

Objective: To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC). Methods: In this single-center, phase II study with open-label, randomized and controlled design, young patients (18–45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate. Results: Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1–94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38–5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate. Conclusion Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead.

Sesquiterpenoids are comprised of three C₅ units and derived from farnesyl diphosphate. In these C₁₅ family of terpenoids, drimane-type sesquiterpenoids are unique as their chemical structure of decahydronaphthalene along with the methyl group decorations resemble the A/B rings of labdane derived diterpenoids and the eastern part of many meroterpenoids. In the past decades, based on their chemical structural features and diverse bioactivities, great efforts have been made to perform chemical and biological research on this family of natural products, leading to the characterization of a large of new compounds and a few biosynthetic pathways. In this review, we collected 164 new drimane-type sesquiterpenoids from fungi between January 2004 and October 2021 and classified them into three major subfamilies, so as to highlight their diverse chemical structures, biological activities, and biosynthetic pathways,.
Polycyclic Sesquiterpenes ; Sesquiterpenes/chemistry* ; Fungi ; Terpenes/chemistry* ; Diterpenes

Objective:To investigate the preparation methods and quality control of 177Lu-labeled radiopharmaceuticals, and conduct preliminary clinical application research. Methods:177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-Phe1-Tyr3-octreotide (TOC) and 177Lu-prostate specific membrane antigen (PSMA)-I&T were labeled by manual labeling and automatic labeling, respectively. Factors such as the amount of precursor and nuclide, reaction temperature, pH value, reaction time, labeling yield and specific activity were investigated. Quality control of the products were carried out, such as clarity, pH value, sterility, bacterial endotoxin and stability in vitro. 177Lu-PSMA-I&T was applied to the treatment of prostate cancer patients, and the efficacy was evaluated by SPECT/CT imaging. Paired t test was used to analyze the data. Results:The amount of precursor and nuclide, reaction temperature, pH value and reaction time of the two methods were basically the same, both with high yield and specific activity. The yield of 177Lu-DOTA-TOC automatic labeling was significantly higher than that of manual labeling (99.2±0.4)% vs (95.3±1.5)% ( t=7.17, P<0.001), and the specific activity were (91.6±13.7) vs (89.1±13.2) GBq/μmol. The yield of 177Lu-PSMA-I&T automatic labeling was also significantly higher than that of manual labeling (99.6±0.3)% vs (95.7±1.3)% ( t=8.24, P<0.001), and the specific activity were (96.1±14.3) vs (93.2±13.8) GBq/μmol. The labeled products were colorless clear solution with pH value of 6.5-7.0. The sterility and bacterial endotoxin met the requirements. The radiochemical purity of the labeled products was more than 95% after 48 h, which showed good stability. The clinical application of 177Lu-PSMA-I&T in patients with prostate cancer showed that both primary and metastatic lesions had good uptake. Conclusions:The labeling of 177Lu radiopharmaceuticals is simple and has high yield and stability. The application of automatic labeling can simplify the process, improve the yield and reduce irradiation.

Objective:To prepare pH-sensitive liposomes to avoid the degradation of monophosphoryl lipid A (MPLA) by lysosomes.Methods:Using DOPE and CHEMS as carrier materials, pH-sensitive liposomes were prepared by thin-film dispersion method. Particle sizes and Zeta potential of the liposomes were detected by dynamic light scattering. The morphological features of pH-sensitive liposomes under different pH conditions were observed by transmission electron microscopy. Flow cytometry was performed to detect the phagocytosis of liposomes by THP-1 and DC2.4 cells. Confocal laser microscopy was used to observed the colocalization of liposomes and lysosomes. BALB/c mice were immunized with hepatitis B surface antigen (HBsAg) using MPLA pH-sensitive liposome as an adjuvant. The levels of serum anti-HBs were quantitatively detected by ELISA. IFN-γ and IL-2 spot forming cells (SFCs) in mouse splenic lymphocytes were detected by ELISPOT.Results:The pH-sensitive liposomes were constructed with an average particle size of (90.90±1.13) nm, polydispersity index (PDI) of 0.076±0.013 and Zeta potential of (-27.900±0.666) mV. As the pH value of the solution decreased, the particle size increased significantly and the liposomes presented irregular shapes, indicating the pH-sensitive features. The phagocytosis rates by THP-1 cells and DC2.4 cells were 10.40% and 12.40% for pH-sensitive fluorescent liposomes, and 1.09% and 0.28% for fluorescent liposomes. Confocal laser microscopy revealed that pH-sensitive fluorescent liposomes were phagocytosed by THP-1 cells and existed in the cytoplasm, while fluorescent liposomes existed in lysosomes. Compared with MPLA liposomes, MPLA pH-sensitive liposomes could significantly improve the cellular immune response in mice. The levels of IFN-γ and IL-2 SFCs in the MPLA pH-sensitive liposome group were significantly higher than those in the MPLA liposome group ( P<0.01) and the non-adjuvant group ( P<0.001). Conclusions:The pH-sensitive liposome delivery system could improve the utilization of MPLA as an adjuvant.

Objective:To build a small-sample ultra-widefield fundus images (UWFI) multi-disease classification artificial intelligence model, and initially explore the ability of artificial intelligence to classify UWFI multi-disease tasks.Methods:A retrospective study. From 2016 to 2021, 1 608 images from 1 123 patients who attended the Eye Center of the Renmin Hospital of Wuhan University and underwent UWFI examination were used for UWFI multi-disease classification artificial intelligence model construction. Among them, 320, 330, 319, 268, and 371 images were used for diabetic retinopathy (DR), retinal vein occlusion (RVO), pathological myopia (PM), retinal detachment (RD), and normal fundus images, respectively. 135 images from 106 patients at the Tianjin Medical University Eye Hospital were used as the external test set. EfficientNet-B7 was selected as the backbone network for classification analysis of the included UWFI images. The performance of the UWFI multi-task classification model was assessed using the receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, and accuracy. All data were expressed using numerical values and 95% confidence intervals ( CI). The datasets were trained on the network models ResNet50 and ResNet101 and tested on an external test set to compare and observe the performance of EfficientNet with the 2 models mentioned above. Results:The overall classification accuracy of the UWFI multi-disease classification artificial intelligence model on the internal and external test sets was 92.57% (95% CI 91.13%-92.92%) and 88.89% (95% CI 88.11%-90.02%), respectively. These were 96.62% and 92.59% for normal fundus, 95.95% and 95.56% for DR, 96.62% and 98.52% for RVO, 98.65% and 97.04% for PM, and 97.30% and 94.07% for RD, respectively. The mean AUC on the internal and external test sets was 0.993 and 0.983, respectively, with 0.994 and 0.939 for normal fundus, 0.999 and 0.995 for DR, 0.985 and 1.000 for RVO, 0.991 and 0.993 for PM and 0.995 and 0.990 for RD, respectively. EfficientNet performed better than the ResNet50 and ResNet101 models on both the internal and external test sets. Conclusion:The preliminary UWFI multi-disease classification artificial intelligence model using small samples constructed in this study is able to achieve a high accuracy rate, and the model may have some value in assisting clinical screening and diagnosis.