Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

ObjectiveTo analyze the research situation， hotspots， and trend of the compatibility of bitter and pungent medicinals in traditional Chinese medicine by knowledge mapping and provide reference for the inheritance and clinical application of this theory. MethodsThe literature on the compatibility of bitter and pungent medicinals was retrieved from 6 databases， including China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， SinoMed， Web of Science， and PubMed. The literature was searched with the keywords of bitter medicinals， pungent medicinals， compatibility， Banxia Xiexin decoction， Zhuyu pills， and Zuojin pills. The search time ranged from January 1， 1984 to August 10， 2024. NoteExpress 3.7 was used for literature screening， and CiteSpace 6.1.R2 was used to visualize the number of publications， authors， institutional cooperation network， and the co-occurrence， clustering， time line， and burst of keywords. ResultsA total of 628 Chinese articles and 151 English articles related to the compatibility of bitter and pungent medicinals were included， and the annual number of publications rose with fluctuations. WEI Wei was the core author of Chinses articles and SHEN Tao and ZHAO Yanling were the core authors of English articles. China Academy of Chinese Medical Sciences formed a close cooperative network with many research institutions at home and abroad. The high-frequency keywords included pungent dispersing and bitter descending， Coptidis Rhizoma， Euodiae Fructus， Banxia Xiexin decoction， Zuojin pills， compatibility， spleen and stomach diseases， and gut microbiota， which mainly involved common prescriptions， diseases responding specifically to traditional Chinese medicine， mechanism research and so on. The keyword bursts concentrated in famous doctors' experience， network Meta-analysis， inflammatory bowel disease， diabetes mellitus， intestinal microbiota， etc. The compatibility of bitter medicinals and pungent medicinals was widely used in clinical practice. Based on pungent dispersing and bitter descending， the middle energizer was regulated for treating spleen and stomach diseases and inflammatory bowel disease. Bitter and pungent medicinals descending the turbid were used to treat diabetes mellitus and hyperlipidemia by lowering blood glucose and lipid levels. The mild bitter and slightly pungent medicinals were used as supplements to treat depression and COVID-19 by regulating Qi movement. ConclusionIn the past 40 years， the number of publications on the compatibility of bitter and pungent medicinals has been increasing， and the research team has begun to take form. Clinically， the compatibility of bitter and pungent medicinals is the main treatment for spleen and stomach diseases and glycolipid metabolic diseases. At present， the modern scientific essence of the compatibility of bitter and pungent medicinals is mainly explained based on famous doctors' experience inheritance， network meta-analysis， and intestinal flora.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia （syndrome of phlegm turbidity and obstruction） complicated with carotid atherosclerosis. MethodsA total of 120 patients with hyperlipidemia （syndrome of phlegm turbidity and obstruction） complicated with carotid atherosclerosis were randomly allocated into a treatment group and a control group， with 60 patients in each group. The control group orally took rosuvastatin calcium tablets， 10 mg each time， once a day. The treatment group took Zhuyuwan granules， 1 dose a day in 3 times. Both groups received diet and exercise guidance and were treated for 24 consecutive weeks. The traditional Chinese medicine （TCM） symptom scores were recorded before and after treatment. The levels of blood lipids ［total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）］， carotid color ultrasound ［carotid intima-media thickness （IMT）， plaque number， maximum plaque area， and maximum plaque thickness］， vascular intimal repair-related factors ［nitric oxide （NO）， endothelin-1 （ET-1）， soluble intercellular adhesion molecule 1 （sICAM-1）， and thromboxane B2 （TXB2）］， and oxidative stress-related indicators ［superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）］ were measured before and after treatment. The occurrence of adverse reactions was observed during treatment， and the clinical efficacy of the two groups was compared after treatment. ResultsThe trial was completed and 112 patients （57 in the treatment group and 55 in the control group） were included in the statistical analysis， and the general information of the two groups was comparable. The total response rate in the treatment group was 87.72% （50/57）， which was higher than that （74.55%， 41/55） in the control group （χ²=4.823， P<0.05）. After treatment， the scores of main TCM symptoms such as body obesity， chest tightness， and limb numbness， the scores of secondary symptoms such as palpitation， insomnia， tastelessness in the mouth， reduced appetite， tongue and pulse manifestation scores， and the total TCM symptom score decreased in both groups （P<0.05， P<0.01）. Moreover， the treatment group had lower scores of main symptoms such as body obesity， head heaviness， chest tightness， nausea， salivation， and limb numbness， scores of secondary symptoms such as tastelessness in the mouth and reduced appetite， and total TCM symptom score than the control group （P<0.05， P<0.01）. After treatment， both groups showed declines in TC， TG， LDL-C， IMT， plaque number， maximum plaque area， maximum plaque thickness， ET-1， sICAM-1， and TXB2 （P<0.05， P<0.01） and elevations in levels of HDL-C， NO， and SOD （P<0.05， P<0.01）. The treatment group had lower TC， TG， LDL-C， IMT， plaque number， maximum plaque area， maximum plaque thickness， ET-1， sICAM-1， and TXB2 （P<0.01） and higher levels of HDL-C， NO， SOD， and GSH-Px （P<0.05， P<0.01） than the control group. During treatment， adverse reactions occurred in 3 cases （5.26%， 1 case of dizziness， 1 case of acid reflux， and 1 case of constipation） in the treatment group and 4 cases （7.27%， 2 cases of upper respiratory tract infection， 1 case of abdominal pain， and 1 case of low back pain） in the control group. ConclusionZhuyuwan can effectively reduce blood lipid levels， inhibit the formation of carotid atherosclerotic plaque， and alleviate the syndrome of phlegm turbidity and obstruction by promoting vascular intima repair and improving the antioxidant function.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Objective To optimize the process conditions and analyze the components of alkaloids from Zanthoxylum bungeanum Maxim（Z. bungeanum）using macroporous resin. Methods Combining single factor tests and orthogonal tests, the content of hydroxy-α-sanshool（HAS）and hydroxy-β-sanshool（HBS）were considered as indexes to determine the best process parameters. Ultra-performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E）was used to identify the structures of alkaloids. Results The optimal conditions were Mitsubishi HP-20 macroporous resin, the loading solution concentration was 0.2 g crude drug/ml, the ratio of crude drug to resin volume was 1 g∶2.5 ml, the diameter/height ratio of resin column was 1∶7, the dynamic adsorption flow rate was 4 times of bed volume（BV）per hour, and the adsorption time was 1 h. Impurities were removed by using 2 BV of 20% ethanol, 5 BV of 80% ethanol was used to elution, and the content of HAS and HBS was 4.71% and 1.02%, respectively. A total of 20 alkaloids were identified from Z. bungeanum. Conclusion This method was stable and feasible, obtaining high purity and various kinds of alkaloids, which could be used for the enrichment and purification of alkaloids from Z. bungeanum.

ObjectiveTo explore the effect of exercise on anxiety and depression in cancer patients during chemotherapy, as well as the optimal exercise dosage. MethodsA PICO framework was constructed, and randomized controlled trials (RCTs) on the effect of exercise on anxiety and depression in cancer patients during chemotherapy were retrieved from databases of PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang data, from the establishment to November, 2023. The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database (PEDro) scale. Data were synthesized and analyzed using RevMan 5.3, and the risk of bias was evaluated using Stata 18.0. ResultsA total of 13 RCTs involving 1 340 subjects were included. The scores of PEDro scale were five to eight. Exercise interventions significantly improved anxiety (SMD = -0.70, 95%CI -1.18 to -0.22, P = 0.004) and depression (SMD = -0.89, 95%CI -1.43 to -0.34, P = 0.002) compared to the control group. Subgroup analyses showed that, the exercise effect on anxiety was less than 45 minutes a time (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), more than three times a week (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), and less than twelve weeks (SMD = -0.21, 95%CI -0.36 to -0.07, P = 0.005). For depression, it was less than 45 minutes a time (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), more than three times a week (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), and less than twelve weeks (SMD = -0.52, 95%CI -0.92 to -0.13, P = 0.01). Moderate to high-intensity exercise interventions significantly outperformed the control group in improving anxiety (SMD = -0.21, 95%CI -0.37 to -0.06, P = 0.007) and depression (SMD = -0.21, 95%CI -0.41 to -0.01, P = 0.04). ConclusionExercise interventions can effectively improve anxiety and depression in cancer patients during chemotherapy, and it suggests for high-intensity exercise, less than 45 minutes a time, more than three times a week, and less than twelve weeks.

BackgroundAggressive behavior in schizophrenic patients could result in legal disputes and public safety concerns. In patients with illness episodes of different numbers， there may exist differences in the association between levels of novel inflammatory indicators and aggressivity. ObjectiveTo investigate the differences in the correlation between levels of novel inflammatory indicators and aggressivity in patients with first-episode and recurrent schizophrenia， in order to search for inflammatory biomarkers to assess aggression level in schizophrenic patients. MethodsA total of 168 schizophrenic patients were selected as subjects， who were hospitalized for acute disease onset in Chaohu Hospital of Anhui Medical University from October 2022 to April 2024 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into first-episode group （n=58） and recurrent group （n=110）. Meanwhile， 110 healthy controls from community who matched in age and gender with the patient group were recruited. All patients were evaluated with Modified Overt Aggression Scale （MOAS） and Positive and Negative Syndrome Scale （PANSS）. All subjects went through examination of the levels of novel inflammatory indicators， including neutrophil/lymphocyte ratio （NLR）， monocyte/lymphocyte ratio （MLR）， platelet/lymphocyte ratio （PLR）， neutrophil/high-density lipoprotein ratio （NHR）， monocyte/high-density lipoprotein ratio （MHR） and platelet/high-density lipoprotein ratio （PHR）. Spearman correlation analysis was adopted to investigate the correlation between levels of novel inflammatory indicators and the total score of MOAS in patients with first-episode and recurrent schizophrenia. ResultsThe levels of NLR， MLR， PLR， NHR， MHR and PHR in first-episode group were higher than those in control group （adjusted P<0.01）. The levels of NLR， MLR， NHR， MHR and PHR in recurrent group were higher than those in control group （adjusted P<0.01）. No significant difference was observed in the comparison in the levels of six novel inflammatory indicators between first-episode group and recurrent group （adjusted P>0.05）. Spearman correlation analysis showed， the MOAS total score of recurrent group was positively correlated with the levels of NLR， MLR and PLR （r=0.234， 0.192， 0.243， P<0.05）. There was no statistical significance in the correlation between MOAS total score and levels of six novel inflammatory indicators in first-episode group （P>0.05）. ConclusionAmong patients with first-episode and recurrent schizophrenia， the correlation between levels of novel inflammatory indicators and aggressivity could differ. NLR， MLR and PLR might be the biomarkers for assessing aggression level in recurrent schizophrenic patients. ［Funded by Anhui Provincial Natural Science Foundation （number， 2108085MH275）］

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.