“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus （GDM） model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank， model， insulin detemir （20 U·kg^-1） and Zuoguiwan （1.89 g·kg^-1） groups （n=18）. GDM was induced by peritoneal injection of streptozotocin on day 6.5 （E6.5d） in the embryonic stage， and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group， pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored， and the embryos and offspring rats were measured for the length and weighed on E12.5d， E18.5d and day 21 after birth （B21d）. The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the fasting insulin （FINS） levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance （HOMA-IR） was calculated. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total bilirubin （TBIL）， total cholesterol （CHO）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL） in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d， E18.5d and B22d rats were observed by hematoxylin-eosin （HE） staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 （Pdx1）， pancreas-specific transcription factor 1a （Ptf1a）， and sex-determining region Y-box protein 9 （Sox9） in the pancreas of E12.5d embryos， Pdx1， Nkx2 homeobox 2 （Nkx2.2）， and hairy and enhancer of split-1 （Hes1） in the pancreas of E18.5d embryos， and Pdx1， v-maf musculoaponeurotic fibrosarcoma oncogene homolog A （Mafa）， and NK transcription factor-related homeobox gene family 6 locus 1 （Nkx6.1） in the pancreas of B22d rats. ResultsCompared with the blank group， the model group showed elevated blood glucose levels in pregnant rats on B0d， E9.5d， E12.5d， E15.5d， and E18.5d （P<0.05， P<0.01）， decreased body weight and body length （P<0.01） and increased Lee's index in the offspring. In addition， the B22d offspring showed rising levels of FBG， FINS， HOMA-IR， AST， and TG （P<0.01）， a declined level of HDL （P<0.01）， and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT， AST， and TG （P<0.05， P<0.01） in the pancreas and a declined level of HDL （P<0.05）. The E12.5d embryos showed up-regulated protein levels of Pdx1， Sox9， and Ptf1a in the pancreas （P<0.01） and the E18.5d embryos exhibited down-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas （P<0.01）. The protein levels of Pdx1， Nkx6.1， and Mafa in the pancreas of B22d offspring were down-regulated （P<0.01）. Compared with the model group， the insulin group exhibited lowered blood glucose in pregnant rats on B0d， E15.5d， and E18.5d （P<0.05， P<0.01）. The offspring in all treatment groups showcased increased body weight and body length （P<0.01） and decreased Lee's index. The B22d offspring exhibited declined levels of FBG， FINS， and HOMA-IR in the insulin group （P<0.01） and lowered levels of FBG and HOMA-IR in the Zuoguiwan group （P<0.01）. The B22d offspring in all the treatment groups showed reduced levels of ALT， AST， TBIL， CHO， TG， and LDL， a raised level of HDL， and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT （P<0.05， P<0.01） and an elevated level of HDL （P<0.05）. The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group （P<0.05）. The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1， Sox9， and Ptf1a （P<0.01）. All the treatment groups showed up-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas of E18.5d embryos （P<0.01） and Pdx1， Nkx6.1， and Mafa in the pancreas of B22d embryos （P<0.05， P<0.01）. ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.

OBJECTIVE To improve the quality standard of Zhuang medicine Yingbupu （Aralia armata）. METHODS A total of 23 batches of Yingbupu （A. armata） were studied. Their macroscopic characteristics and powder microscopic features were observed. TLC was employed for the qualitative identification of oleanolic acid and araloside A. Items such as water content， total ash， acid-insoluble ash， and ethanol-soluble extract were determined according to the methods specified in the 2020 edition of the Chinese Pharmacopoeia （part Ⅳ）. UPLC fingerprint was established for 23 batches of samples by using Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）， and the contents of oleanolic acid and araloside A were determined. RESULTS The powder microscopic characteristics of the medicinal material were distinctive. Oleanolic acid and araloside A were detected by TLC in all 23 batches. Among the 23 batches of samples， the content ranges of moisture， total ash， acid-insoluble ash， and ethanol-soluble extract were 6.9% to 10.4%， 1.8% to 6.8%， 0.1% to 1.9%， and 2.8% to 8.4%， respectively. Based on the UPLC fingerprint， a total of 15 common peaks were obtained， and 9 of these common peaks were identified. The content ranges of oleanolic acid and araloside A in the 23 batches of samples were 0.86% to 2.69% and 0.16% to 1.10%， respectively. CONCLUSIONS This study has added items such as moisture and total ash content fingerprint， TLC identification. A preliminary quality standard has been established for the medicinal material of Yingbupu （A. armata）， stipulating that the moisture content should not exceed 11.0%， the total ash content should not exceed 5.0%， the acid-insoluble ash content should not exceed 2.5%， the ethanol-soluble extract（No. content should not be less than 4.0%， and the contents of zyyzdxk-2023165） oleanolic acid and araloside A should not be less than 1.00% and 0.45%（ calculated by a dried basis）， respectively.

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

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

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objectives:This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs).Methods:The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit).Results:All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively.Conclusions:This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.