Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

【Objective】 To investigate the psychological status of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and to analyze the effects of anxiety on the total National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) in patients in Ngari Prefecture of Tibet. 【Methods】 CP/CPPS patients treated during Oct.2019 and Oct.2021 were involved and divided into anxiety group and non-anxiety group. The non-anxiety group received routine drug treatment, while the anxiety group received drugs and psychological intervention. 【Results】 A total of 117 patients were involved, including 68 in the anxiety group and 49 in the non-anxiety group. There were no statistical differences between the two groups in terms of age, body mass index (BMI), marital status, smoking history, and education level (P>0.05). The total NIH-CPSI score in the anxiety group (18.53±3.47) was higher than that in non-anxiety group (15.67±3.33), which was mainly manifested by the increase of pain and decrease of quality of life scores. Further stratification of anxiety level revealed that quality of life score and total NIH-CPSI score increased as anxiety symptoms worsened. After drug treatment, pain and urination symptoms were improved in the non-anxiety group, but the quality of life score and total NIH-CPSI score did not change significantly. After psychological intervention, the anxiety group had lower total NIH-CPSI score and other scores. 【Conclusion】 It is not uncommon for CP/CPPS patients to have a comorbidity of anxiety. The increase in the total NIH-CPSI score is caused by the increase of pain score and decrease of quality of life score. Active psychological intervention can improve anxiety, urinary symptoms, pain symptoms and quality of life.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective:To conduct quality evaluation and content analysis of adult postoperative nausea and vomiting (PONV) guidelines, so as to provide reference for management of clinical PONV.Methods:Web of Science, Embase, PubMed, UpToDate, SinoMed, Wanfang Database, China National Knowledge Infrastructure, VIP, domestic and foreign clinical practice guidelines and related professional association websites were systematically searched, and the search period was from database establishment to May 6, 2022. Four researchers independently evaluated the guidelines that met the inclusion and exclusion criteria using a clinical guideline research and evaluation system, and summarized the recommendations of the guidelines.Results:Finally, a total of 15 guidelines were included in this study. The overall quality evaluation of the guide was 3 A-level recommendations and 12 B-level recommendations. The average standardization percentages for 6 areas were 81.57% for scope and purpose, 49.91% for participants, 65.38% for rigor, 89.54% for clarity, 34.86% for applicability and 55.42% for independence. A total of 18 recommendations were summarized from five aspects, such as team and organizational management, PONV risk assessment, baseline risk reduction, multimodal prevention of PONV and effectiveness evaluation and monitoring.Conclusions:The guidelines for PONV management mainly come from foreign countries. It is recommended that clinical personnel should learn from foreign guidelines and combine them with domestic clinical situations to localize the recommended opinions and guide the development of clinical practice.

The patient, a 19-year-old female, found that the blue and purple mass was in her left forearm 3 years ago, and the mass gradually increased without obvious pain. It disappeared when pressing. The first diagnosis was "left forearm venous malformation" . During the operation, the boundary of the tumor body was clear and the capsule was complete. The blood supply of the tumor body was very rich. There were many micro capillary networks in the tumor body. It looked like "venous malformation" by general observation. But it was diagnosed as subcutaneous hamartoma by pathological examination. It was very similar to venous malformations by preoperative and intraoperative clinical manifestations, which will lead to misdiagnosis. Therefore, we should carefully handle and broaden the thinking of disease analysis in the similar cases.

The patient, a 19-year-old female, found that the blue and purple mass was in her left forearm 3 years ago, and the mass gradually increased without obvious pain. It disappeared when pressing. The first diagnosis was "left forearm venous malformation" . During the operation, the boundary of the tumor body was clear and the capsule was complete. The blood supply of the tumor body was very rich. There were many micro capillary networks in the tumor body. It looked like "venous malformation" by general observation. But it was diagnosed as subcutaneous hamartoma by pathological examination. It was very similar to venous malformations by preoperative and intraoperative clinical manifestations, which will lead to misdiagnosis. Therefore, we should carefully handle and broaden the thinking of disease analysis in the similar cases.

OBJECTIVE：To pre pare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles （GA-DTX-NGO/IONP- NPs），and to evaluate its physicochemical properties. METHODS ：Magnetic nano graphene oxide （NGO/IONP）was chosen as the anti-tumor drug carrier ，docetaxel（DTX）as the model drug and glycyrrhetinic acid （GA）as the target molecule. Firstly ，NGO/ IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction. Fourier IR spectrometer ，DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS. GA-DTX-NGO/IONP-NPs Huperzine A in the nicotinic acetylcholine receptor alleviates Aβ -induced 1-42 treatment of Alzheimer ’s disease and vascular dementia ：a neurotoxicity via downregulation of p 38 and JNK MAPK meta-analysis[J]. Evid Based Complement Alternat Med ， signaling pathways[J]. Neurochem Int ，2018. DOI ：10. 2014. DOI ：10.1155/2014/363985. 1016/j.neuint.2018.09.005. were prepared by the ion gelation method. TEM and particle size analyzer were used to observe and determine the morphology ， particle size and Zeta potential of GA-DTX-NGO/IONP-NPs ；the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount ；the magnetic properties were investigated by investigating the state with or without external magnetic field ；the photothermal conversion test was carried out with laser irradiation of 808 nm. RESULTS ：NGO/ IONP and GA-CS were successfully synthesized ，and NGO/IONP exhibited superparamagnetism characteristics. GA-DTX-NGO/ IONP-NPs were spherical under TEM ，the particle size was （262.8±4.23）nm and the Zeta potential was （13.6±1.51）mV. The encapsulation rate and drug loading amount were （94.29±0.50）％ and（17.12±0.12）％，respectively. GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed. Under the external magnetic field ，the magnetic nanoparticles could move directionally，showing good magnetic properties. GA-DTX-NGO/IONP-NPs showed a good concentration- and time-dependent photothermal conversion effect under 808 nm laser irradiation. CONCLUSIONS ：GA-DTX-NGO/IONP-NPs are successfully prepared. This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.

OBJECTIVE： To optimize and improve the quality standard for Citrus reticulata formula granules. METHODS： Totally 13 batches of C. Reticulata formula granules from 4 different manufacturers were used as trial samples， and qualitative identification of hesperidin and nobiletin in the samples were carried out by TLC according to the method of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. The quantitative analysis of naringin， hesperidin， hesperetin， nobiletin and tangeretin in C. reticulatae formula granules were conducted by UPLC[The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid aqueous solution （gradient elution）. The detection wavelength was set at 283 nm， and sample size was 3 μL]. RESULTS： The results of TLC showed that in the chromatograms of samples， same color spots were shown in the corresponding positions of the chromatogram of reference substance. The results of UPLC showed， that the linear range of naringin， hesperidin， hesperetin， nobiletin and tangeretin were 0.64-6.44， 15.78-157.80， 0.17-1.66， 2.08-20.85 and 2.04-20.43 μg/mL， respectively （all r≥0.999 2）； the limits of detection were 0.03， 0.33， 0.10， 0.20 and 0.06       μg/mL； the limits of quantitation were 0.07， 1.34， 0.20， 0.60 and 0.22 μg/mL. The average recoveries were 99.4％， 99.6％， 99.7％， 99.7％ and 99.7％ （n＝9）； RSDs of precision （n＝6）， stability （n＝7） and reproducibility （n＝6） tests were all≤2.03％； naringin was detected in only 3 batches of samples from one manufacturer （the content ranged from 0.067 3 to 0.069.6    mg/g）， while the other 4 components were detected in 13 batches of samples （the contents of them ranged 0.646 5-1.728 0，   0.102 6-0.290 5， 0.023 1-0.689 8， 0.018 2-0.270 7 mg/g）. CONCLUSIONS： In this study， the quality standard of C. reticulata formula granules was improved by qualitative and quantitative methods， and the contents of hesperidin， hesperetin， nobiletin and tangeretin were not less than 0.60， 0.10， 0.02 and 0.01 mg/g， respectively.

OBJECTIVE： To establish UPLC fingerprint of Fortunella margarita， and to conduct its cluster analysis and principal component analysis. METHODS： UPLC method was adopted. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution （gradient elution） at the flow rate of 0.3 mL/min. The detection wavelength was set at 330 nm， and sample size was 2 μL. Using fortunellin as reference， UPLC fingerprints of 8 batches of F. margarita were determined. The similarity of 8 batches of samples was evaluated by TCM Chromatographic Fingerprint Similarity Evaluation System（2012 edition） to confirm common peak. Cluster analysis and principal component analysis were performed by using SPSS 24.0 software. RESULTS： There were 24 common peaks in UPLC fingerprints of 8 batches of sample，the similarity of which was higher than 0.97. Cluster analysis showed that 8 batches of samples were clustered into 2 categories. S1， S2， S3， S4， S6， S7 and S8 were clustered into one category； S5 was clustered into the other category. By principal component analysis， the accumulative contribution rate of three main components was 81.366％. CONCLUSIONS： Established UPLC fingerprint， the results of cluster analysis and principal component analysis can provide reference for quality control of F. margarita.