ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer deaths. Lung adenocarcinoma is the most common type of lung cancer. Due to the lack of effective biomarkers and therapeutic targets in the proliferation and metastasis of lung adenocarcinoma, the overall treatment of lung adenocarcinoma is not optimistic. Therefore, there is a need to find new ideas and methods for lung adenocarcinoma treatment. The 26S proteasome is a multiprotein complex responsible for degrading misfolded proteins and maintaining intracellular protein homeostasis. During the development of non-small cell lung cancer (NSCLC), the regulatory granule subunit of the 26S proteasome promotes the malignant progression of tumours by regulating tumour-associated proteins, immune cells, and related signalling pathways. The proteasome core particle is a key subunit for degrading proteins, and its inhibitors have shown promising anti-tumour effects when combined with conventional chemotherapeutic agents. However, limited by toxic side effects and tumour heterogeneity, targeted inhibitors against the 26S proteasome are still not widely used in NSCLC treatment. This article reviews the mechanism of action and related therapeutic research of 26S proteasome regulatory particle subunits and core particle subunits in NSCLC, and explores the potential of these inhibitors in clinical application.
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Humans ; Proteasome Endopeptidase Complex/chemistry* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Animals ; Proteasome Inhibitors/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Objective To investigate the effects of transcranial direct current stimulation(tDCS)on the topologic attributes of brain functional network in the patients with mild cognitive impairment(MCI).Meth-ods Thirty-three included patients with MCI were randomly divided into the real stimulation group(18 ca-ses)and pseudo-stimulation group(15 cases).All patients received the tDCS treatment for consecutive 10 d.The left dorsolateral prefrontal cortex(DLPFC)was stimulated by the anode,while the right orbital socket DLPFC was stimulated by the cathode.The neuropsychological scale assessment and resting state functional magnetic resonance imaging(rs-fMRI)image collection were performed before and after treatment.The GRETNA software was used to preprocess the rs-fMRI images and analyze the graph theory.The Pearson correlation analysis was used to calculate the correlation between behavioral indicators and network attribute indicators of significant difference between the two groups.Results There were statistically significant differ-ences in the node attributes(intermediate number centrality,degree centrality and local efficiency of nodes)before and after treatment,and between the two groups after treatment(P＜0.05).Compared with before treatment,the scores of MMSE,MoCA,AVLT-N7 and BNT after treatment in the real stimulation group were significantly increased[(25.89±2.16)points,(21.16±2.77)points,(4.95±1.81)points,(19.47±3.13)points].Conclusion tDCS could effectively regulate the local topological attributes of nodes in the cognitive-related brain region of MCI and improve the cognitive function.

Objective To retrieve,evaluate and summarize the relevant evidence on malnutrition management among maintenance hemodialysis(MHD)patients to provide clinical medical staff with evidence-based guidelines for managing malnutrition in MHD patients.Methods Using the"6S"pyramid model of evidence,We searched UpToDate,BMJ best clinical practice,the Australian JBI evidence-based health care centre database(JBI),Medive,the International Guidelines Collaborative Network(GIN),Agency for Healthcare Research and Quality Network,the UK National Institute of Clinical Medicine Guidance Library(NICE),Scottish Inter-College Guide Collaboration network,the Ontario Registered Nurses Association(RNAO),Guidelines Network of International Society of Nephrology,American Nephrology Foundation Guidenet,British Nephrology Society,Society of Nephrology,Chinese Medical Association,Improving Kidney Disease Outcomes Worldwide,International Society of Renal Nutrition and Metabolism,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Nutrition Society,PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and CBM,to collect relevant guidelines,expert consensus,clinical decision,evidence summary,recommended practice,best practice,systematic evaluation and clinical practice,from the establishment to the date of April 10th,2023,for literature on malnutrition management of MHD patients.The literature included guidelines,expert consensuses,clinical decision-making studies,evidence summaries,recommended practices,best practices,and systematic reviews.Two researchers independently evaluated,extracted,and integrated the evidence.The evidence was graded by the evidence pre-grading system of the Evidence-based Healthcare Center of Joanna Briggs Institute(JBI).Results A total of 16 articles were included and summarized,comprising 5 guidelines,3 expert consensuses,1 clinical decision-making study,1 evidence summary,and 6 systematic reviews.Thirty-nine pieces of the best evidence were integrated,covering 5 key aspects(39 evidences):screening and assessment,nutritional requirements,nutritional supplement,other interventions,and monitoring and education.Conclusions The best evidence summary of malnutrition management among MHD patients in this study is scientifically rigorous and systematic.Clinical medical staff can use the best evidence to develop personalized malnutrition management programs for MHD patients.

OBJECTIVE To systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2 diabetes mellitus. METHODS PubMed， Cochrane Library， Web of Science， Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo （or other oral hypoglycemic agents） in the treatment of type 2 diabetes were included， data were extracted and meta-analysis was analyzed using RevMan 5.4 software. RESULTS A total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect， compared with control group， glucokinase activators significantly reduced glycosylated hemoglobin （HbA1c） [MD＝－0.40， 95%CI（－0.53， －0.26）， P＜0.000 01]， fasting blood glucose[MD＝－0.53， 95%CI（－0.85， －0.20）， P＝0.001] and 2 h postprandial blood glucose [MD＝－2.28， 95%CI（－2.68， －1.88）， P＜0.000 01] in diabetic patients. In terms of safety， the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR＝1.55， 95%CI（1.20，2.01）， P＝ 0.000 8]. According to the subgroup analysis of organs activated by glucokinase activator， the incidence of hypoglycemia in the pancreas-liver dual activator group [RR＝1.44， 95%CI（1.11，1.89）， P＝0.007] and liver-selective activator group [RR＝2.26， 95%CI（1.02，5.03）， P＝0.05] was higher than that in the control group， the difference was statistically significant. CONCLUSIONS Glucokinase activators can effectively reduce HbA1c， fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes， but the risk of hypoglycemia remains to be addressed.

Objective To analyze the target volume margins and positioning errors in the radiotherapy for nasopharyngeal carcinoma(NPC)using the cone-beam computed tomography(CBCT)of Halcyon linear accelerator for providing a reference for the margin from clinical target volume to planning target volume(CTV-to-PTV margin)in the radiotherapy for NPC using Halcyon linear accelerator,hence improving treatment precision and effectiveness.Methods A total of 117 NPC patients who received volumetric modulated arc therapy using Halcyon linear accelerator from May 2020 to June 2022 in Jinshazhou Hospital of Guangzhou University of Chinese Medicine were enrolled.The 3861 CBCT images collected from the patients were matched with the CT images to obtain the correction values of the treatment couch in lateral(Lat),longitudinal(Lng)and vertical(Vrt)directions for positioning error analysis.The CTV-to-PTV margin was obtained by the equation(margin =2.5∑+0.7δ).Results The positioning errors in the radiotherapy for NPC using Halcyon linear accelerator were 0.10(0.00,0.10)cm,0.10(0.00,0.20)cm and 0.20(0.10,0.30)cm in Lat,Lng and Vrt directions,respectively.The CTV-to-PTV margins in Lat,Lng and Vrt directions were 0.12,0.12 and 0.09 cm,respectively.Conclusion Low positioning errors can be achieved for NPC patients undergoing image-guided treatment using Halcyon linear accelerator.

Objective: To evaluate and describe the changes of core muscle groups based on DAVID spine biomechanics training system in ankylosing spondylitis (AS) patients. Methods: The clinical data of 100 patients of AS and 31 healthy controls were collected. Clinical symptoms, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis measurement index (BASMI), ankylosing spondylitis disease activity (ASDAS), and simultaneous detection of DAVID spine biomechanics training system, simple core muscle fitness test: Eight-grade abdominal bridge, PLANK exercise (flat support), Abdominal static muscle endurance test, Back static muscle endurance test were compared using t-test analysis and spearman correlation analysis. Results: ① Between AS and healthy male control o group, there were significant differences of spinal mobility in forward flexion, right rotation, left rotation (42±13 vs 48±1, 52±14 vs 69±12, 52±13 vs 58±11; all P values <0.05); and significant differences of spinal muscle strength in forward bending force, right rotation force, left rotation force, right bending force (103±42 vs 146±17, 87±34 vs 104±13, 80±35 vs 101±13, 161±55 vs 186±19; all P values <0.05), and significant differences in the left/right rotational force (1.17±0.21 vs 1.02±0.111, P<0.05) of spine balance strength comparison.② Between AS and healthy controls of female group, there were differences in forward bending force (49±23 vs 77±10, P<0.05) of spinal muscle strength; and significant differences in forward bending/backward extension strength, left and right rotation strength (0.32±0.11 vs 0.58±0.21, 1.29±0.21 vs1.03±0.11, all P values <0.05) of spine balance strength; ③ In AS group, the spinal mobility was correlated with age (Rear extension r=-0.28, right flexion r=-0.268, left flexion r=-0.404, right rotation r=-0.367, left rotation r=-0.235; all P values <0.05), course of disease (Rear extension r=-0.354, forward flexion r=-0.283, right flexion r=-0.204, left flexion r=-0.284, right rotation r=-0.339, left rotation r=-0.23; all P values <0.05), body mass index (BMI) (Rear extension r=-0.23, forward flexion r=-0.288, right flexion r=-0.22, left flexion r=-0.201, right rotation r=-0.26, left rotation r=-0.29; all P values <0.05), sacroiliac joint stage(Rear extension r=-0.375, forward flexion r=-0.446, right flexion r=-0.331, left flexion r=-0.367, right rotation r=-0.368, left rotation r=-0.314; all P values <0.05) and BASDAI (Rear extension r=-0.381, forward flexion r=-0.374; all P values <0.05). Spinal muscle strength was correlated with gender (Posterior extensor force r=0.344, flexor force r=0.507, right rotation force r=0.376, left rotation force r=0.399, right flexion force r=0.433, left flexion force r=0.445; all P values <0.05); the left/right spine rotation strength was correlated with gender (r=0.271, P<0.05). ④ In the simple core muscle fitness test, eight-grade abdominal bridge was correlated with spinal muscle strength (Rear extension force r=0.234, right rotation r=0.290, left rotation r=0.219, right flexion r=0.35, left flexion r=0.327; all P values <0.05); PLANK exercise was correlated with spinal muscle strength (Rear extension force r=0.234, right rotation r=0.290, left rotation r=0.219, right flexion r=0.35, left flexion r=0.327; all P values <0.05); abdominal static muscle endurance test was correlated with forward flexion strength (r=0.341, P<0.05); back static muscle endurance test was correlated with spinal mobility (Rear extension r=0.262, forward flexion r=0.23, right rotation r=0.455, left rotation r=0.426, right flexion r=0.387, left flexion r=0.46; all P values <0.05); correlated with spine strength (right flexion r=0.256, left flexion r=0.272; all P values <0.05). Conclusion Compared with healthy people, AS patients have decreased activity, strength and balance of spinal core muscle. There are significant decline in spinal mobility and muscle strength of male AS patients and muscle imbalance of female AS patients. Simple core muscle fitness test could be used in clinic to measure the changes of AS patients'core muscle group.

Objective To investigate the differences of gut microbiota in patients with schizophrenia between onset and remission. Methods Twelve patients with schizophrenia in the stage of onset were selected as the episode group. Thirteen gender-, age-and BMI-matched patients with schizophrenia during the remission period were selected as the control group. The fecal specimens of the two groups were collected for high-throughput sequencing of the 16S rRNA gene, and the gut microbiota differences between the two groups were analyzed. Results The chao index and ace index of gut microbiota was lower in the episode group than in the control group (t=2.385,P=0.026; t=3.068,P=0.005). The relative abundance of Bacteroides was higher and the relative abundance of Prevotella was lower in the episodes group than in the control group (Z=-2.013, P =0.044; Z=-3.427, P=0.001). The relative abundance of the Prevotella was negatively correlated with the PANSS score (r=-0.577, P=0.003). Conclusion Schizophrenia in the stage of acute episode have altered gut microbiota compared with those in the stage of remission and the gut microbiota is significantly corrected with mental symptoms.

Objective To compare the short-term safety and efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of large benign thyroid nodules.Methods A total of 34 patients with large benign thyroid nodules were studied retrospectively,including 13 patients treated with ultrasound-guided RFA and 21 patients treated with MWA between Jun.,2016 and Feb.,2017 in Zhongshan Hospital.The thyroid function parameters,serum antibodies,complications and thyroid nodules volume reduction rate(VRR) were compared between the two groups during the follow-up.Results There were no statistically significant differences(P＞0.05)among those patients before and after treatment in serum free triiodothyronine (fT3),free thyroxine (fT4),thyroid stimulating hormone (TSH),anti-thyroglobulin antibodies (TG-Ab) levels,and thyroid peroxidase antibodies (TPO-Ab).One patient in the MWA group had mild hoarseness after ablation and another patient in the RFA group had intraoperative hemorrhage for about 10 mL.There were no other complications such as neck scar,postoperative infection,skin burns,tracheal and esophageal injury.One day after the ablation,all nodules were showed hypoecho and contrast-enhanced ultrasound proved there was no blood supply.One month after treatment,no statistically significant difference was found in VRR between two groups (23.8％ vs.22.6％,P =0.127).Conclusions RFA and MWA are safe and effective treatments for large benign thyroid nodules,and no significant difference was observed in short-term follow-up.

Objective To analyze results of breast cancer screenings in the Cancer Screening Program in Urban China (CanSPUC) during 2012-2013. Methods In 14 cities of 9 provinces (Eastern Region: Beijing, Hebei, Liaoning, Shandong and Guangdong; Central Region: Heilongjiang and Hunan;Western Region: Chongqing and Gansu), 198 097 women aged 40-69 years who had lived in their cities for ≥3 years were surveyed through a cancer risk assessment questionnaire during 2012-2013. The questionnaires identified women considered to be at high risk for breast cancer, of whom 17 104 received screening examinations, for whom complete records of breast cancer screening and other data were available for 12 440 subjects altogether, including breast ultrasound exams for subjects 40-44 years old. Subjects older than 45 years or in whom breast imaging reporting and data system (BI-RADS) ultrasound had found≥3 lesions also underwent mammography. In this cohort, BI-RADS 3 class was defined as suspicious and BI-RADS ≥4 class as positive. Chi-square tests were used to compare breast cancer screening results by groups. Results As of October 2013, breast cancer screening percentages for the 12 440 subjects for whom full data were available were, by region, Eastern: 55.43% (6 895); Central: 21.45% (2 669); and Western:23.12% (2 876); by age, 40-44 years: 5.50% (684); ≥45 years: 94.50% (11 756). Using BI-RADS, 2018 subjects were found to have 3 lesions (detection rate:16.22%), which were distributed regionally as Eastern:19.00% (1 310 women), Central: 13.75% (367) and Western; 11.86% (341); χ2=91.45, P<0.001; and 289 were found to have≥4 lesions (detection rate:2.32%), which were distributed regionally as Eastern:2.41%(166), Central:1.54%(41) and Western;2.85%(82);χ2=11.04, P=0.004. Women aged 50-54 years had the highest detection rate of BI-RADS 3 lesions at 18.74% (561/2 994), and those aged 40-44 years had the highest detection rate of BI-RADS ≥4 at 2.92% (20/684). Conclusion Detection rates of BI-RADS ≥4 lesions were highest in the Western region and in women aged 40-44 years, and lowest in the Central region and in women aged 60-64 years. Detection rates of BI-RADS 3 lesions were highest in the Eastern region and in women aged 50-54 years and the lowest in the Western region and in women aged 60-64 years.