Based on the typical cases from Case Records as a Guide to Clinical Practice （《临证指南医案》） where YE Tianshi applied the "morning and evening differential treatment"， the main types are summarized as follows. When there is middle-lower interlocking injury， and yin deficiency with wind stirring， the method of restraining and consolidating in the morning can be used to restrict jueyang （厥阳）. For deficiency of the extraordinary vessels and heart-spleen ying （营） impairment， the method of consolidating should be used to raise yang in the morning， while the method of moistening and nourishing ying-yin in the evening is used. For lower jiao （焦） depletion with phlegm turbidity obstructing the orifices， it is recommended to tonify lower jiao in the morning and fortify spleen and dissolve phlegm in the evening. If there is kidney-yin depletion with dampness obstructing the qi， it is suggested to supplement kidney and improve qi reception in the morning， while purify upper jiao in the evening. For deficiency and impairment of the collateral vessels， the method of moistening and nourishing ying-yin in the evening can be used. For heart-spleen qi knot， it is recommended to dissolve phlegm and dispel stasis in the evening. In clinical practice， the same medicinal formula can be used with different methods which change according to the syndrome. Taking Sishen Pills （四神丸） and Yuhu Elixir （玉壶丹） as examples， employing different methods in accordance with the primary and secondary pathomechanisms can help transform complex， multiple pathomechanisms into organized treatment steps， providing ideas for managing complicated syndromes with modern Chinese medicine in clinical practice.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective:To analyze the clinical characteristics，laboratory tests，endoscopic features，treatment，and follow-up of peptic ulcers caused by eosinophilic gastrointestinal disorders（EGIDs）in children，with the aim of improving the level of understanding，diagnosis and treatment of EGIDs in children with the onset of peptic ulcers.Methods:A retrospective analysis was conducted on children admitted to the Department of Gastroenterology，Capital Center for Children's Health，Capital Medical University from January 1st，2019 to October 31st，2023，who underwent complete endoscopic examination. The first examination showed the presence of peptic ulcers（gastric or duodenal ulcers）under the endoscope，and were ultimately diagnosed with peptic ulcers caused by EGIDs through examination and follow-up. The clinical characteristics，laboratory tests，endoscopic results，and treatment follow-up were analyzed.Results:Thirty-five children were EGIDs，22 males and 13 females.Twenty-two cases（62.9%）had abdominal pain as the main symptom.Laboratory tests：17 cases（48.6%）showed a decrease in hemoglobin，15 cases（42.9%）showed an increase in eosinophil count，20 cases（57.1%）tested gastro positive for food allergen specific IgE，and 17 cases（48.6%）showed thickening of the intestinal wall on gastrointestinal ultrasound. Endoscopic features：8 cases（22.9%）showed gastric antral ulcers，including 7 cases（20.0%）with multiple gastric antral ulcers，and 25 cases（71.4%）showed duodenal bulb ulcers.There were 15 cases（42.9%）showed huge ulcers，and 14 cases（40.0%）were located in the duodenal bulb. Comparison of clinical characteristics between children with EGIDs（EGIDs group）and those with peptic ulcers caused by Helicobacter pylori infection（Hp group）：the first clinical symptom in both groups was mainly abdominal pain，but the incidence rate in the EGIDs group was lower（62.9% vs 93.5%），and the weigth for length Z score in the EGIDs group was lower［0（-1.6，0.8）vs 1.1（0，1.9）］，with statistical significance（all P<0.05）. Comparison of laboratory tests：the EGIDs group showed a statistically significant difference in hemoglobin levels［120（101，124）g/L vs 130（100，138）g/L］，eosinophil count［0.28（0.13，0.71）× 10 9/L vs 0.16（0.08，0.22）×10 9/L］，a positive rate of food allergen specific IgE detection（57.1% vs 32.3%），and a positive rate of intestinal wall thickening detected by gastrointestinal ultrasound（48.6% vs 16.1%）compared with the Hp group（all P<0.05）. Comparison of endoscopic examinations：multiple ulcers in the gastric antrum were more common in the EGIDs group than in the Hp group（20.0% vs 0），and the difference was statistically significant（ P<0.05）. Conclusion:For children with peptic ulcers with onset of abdominal pain，with anemia or malnutrition，or multiple ulcers in the gastric antrum and huge ulcers in the duodenal bulb detected by endoscopy，it is recommended to perform multi site biopsies to help diagnose EGIDs early.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. METHODS: A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. RESULTS: Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. CONCLUSION Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals ; Nerve Regeneration/drug effects* ; Mice ; Peripheral Nerve Injuries/physiopathology* ; Male ; Ganglia, Spinal/enzymology* ; Axons/physiology* ; Peroxidase/antagonists & inhibitors* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology* ; Disease Models, Animal ; Strychnine/pharmacology*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].