“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.

Objective:To analyze the genetic characteristics of the complete genome of a strain of human respiratory syncytial virus (HRSV) in Qinghai province in 2024.Methods:A total of 300 samples were collected during 2024 influenza surveillance in Qinghai province sentinel hospitals from patients with fever accompanied by severe respiratory infection symptoms. We used real-time fluorescent quantitative reverse transcription polymerase chain reaction RT-PCR) method to screen out HRSV subtype B (HRSVB) positive specimens, whole genome sequencing was performed on positivespecimens meeting the requirements for the sequencing. After downloading the global representative HRSVB genotypes at GenBank database, sequence alignment was performed, related evolutionary tree was built and the calculation and analyses of genetic distance were done, analyses of HRSVB sequencing of sequence homology of nucleotides, amino acids and amino acid mutation were performed.Results:The first strain in Qinghai, China/qinghai/2024-03 had a complete sequence of 15 140 bp nucleotides, with HRSV′s all structural characteristics, and subtype HRSVA prototype strain Long strains of nucleotide the lowest homology was 80.0%, and subtype HRSVB prototype strain nucleotide homology was above 94.7%. The result indicated that the first strain in Qinghai belonged to HRSVB subtype. Genetic evolution shows China/qinghai/2024-03 and USA/WA-S23450/2021 (OR326803.1) and Germany/2021 (OR795235.1) all belong to a branch, they have the closest relationship. Phylogenetic analysis of G gene showed that the strain belonged to BA9 genotype of HRSVB subtype, and the hypervariable regions of the genome were SH and G genes.Conclusions:In this study, the complete genome sequence of HRSV China/qinghai/2024-03 was obtained for the first time, and the basic molecular structural characteristics were elucidated, which filled the gaps in the gene and amino acid data of HRSV in our province, and also provided a basis for HRSV epidemiology.

Objective:To explore therapeutic efficacy and mechanism of puerarin(PUE)in treating of ulcerative colitis(UC).Methods:Network pharmacology and molecular docking technique were used to screen and analyze targets of PUE in regulating UC.C57BL/6 mice were given free access to 2.5%DSS aqueous solution for 7 days,and influence of PUE on changes in body weight and disease activity index(DAI)score were subsequently observed.Histopathological alterations of colon tissue were observed by HE staining,changes of goblet cell population in colon tissue were evaluated through Alcian blue staining;expressions of inflammatory factors in colon tissue were detected by qRT-PCR and ELISA.Effect of PUE on MODE-K cell viability and apoptosis were assessed by CCK-8 and flow cytometry.Results:A total of 38 common targets of PUE in modulating UC,such as AKT1,TNF,STAT3,CASP3,HIF1A and etc,mainly involving TNF,IL-17 and PI3K-Akt signaling pathway.In vivo experiments confirmed that PUE ameliorated degree of colon shortening,body weight and DAI scores and reduced inflammatory cell infiltration in mice.Besides,expressions of inflammatory factors in colon,such as TNF-α and IL-1β,were inhibited by PUE.Furthermore,in vitro experiments validated that PUE relieved DSS-induced apoptosis of epithelial cells.Conclusion:PUE alleviates occurrence and development of DSS-induced UC in mice.

TGF-β1 is considered a key mediator in the formation of hepatic fibrosis and mainly acts by activating the downstream Smad signaling pathway.Smad2 and Smad3 are two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,while Smad7 is a negative-feedback regulator of the TGF-β1/Smad pathway and inhibits TGF-β1-mediated hepatic fibrosis.A growing number of studies are showing that natural products can delay the progression of hepatic fibrosis by regulating the TGF-β1/Smad pathway,inhibiting HSC activation,and reducing ECM deposition.This article reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in hepatic fibrosis,and summarizes the natural products that target the regulation of this pathway,providing a reference for research into the treatment of hepatic fibrosis.

Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.

Objective To investigate the efficacy of methylprednisolone in preventing postoperative pulmonary infections in locally advanced esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy.Methods A total of 89 patients with locally advanced esophageal cancer treated at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023 were selected as the research subjects.All patients underwent thoracolaparoscopic radical esophagectomy for esophageal cancer.The patients were randomly divided into an observation group(n=45)and a control group(n=44)using a random number table method.In the observation group,one patient with intraoperative thoracotomy,two patients with extensive pleural adhesion,and one patient with preoperative upper respiratory tract infection were excluded.In the control group,one patient with extensive pleural adhesion and one patient with preoperative upper respiratory tract infection were excluded.As a result,a total of 83 patients were included in the study,with 41 in the observation group and 42 in the control group.Preoperatively,a neoadjuvant treatment regimen of paclitaxel(albumin-bound)+nedaplatin in combination with camrelizumab was given to patients in both groups for 2 cycles.Patients in the control group received conven-tional anti-infection treatment after surgery,while patients in the observation group were intravenously injected with methylpred-nisolone at a dose of 1 mg·kg-1 daily from the first to the third day after surgery.Postoperative inflammatory markers,incidence of postoperative pulmonary infections,incidence of anastomotic fistula,postoperative hospital stay,and total hospitalization costs were compared between the two groups.Results There were no statistically significant differences in leukocyte count,neutrophil ratio,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6)levels of patients between the two groups before treatment(P＞0.05).On day 1 and 4 after treatment,patients in the observation group had significantly higher leu-kocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels compared to those before treatment(P＜0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels were significantly lower than those on day 1 postopera-tively(P＜0.05).On postoperative days 1 and 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP and IL-6 levels of patients in the control group were significantly higher than those in the preoperative period(P＜0.05),and the leukocyte count,neutro-phil ratio and hs-CRP level were significantly lower on day 4 after surgery than on day 1 after surgery(P＜0.05);the differe-nces in PCT and IL-6 level of patients between day 4 after surgery and day 1 after surgery were not statistically significant(P＞0.05).On postoperative day 1,there were no statistically significant differences in leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels between patients in the observation group and the control group(P＞0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of pulmonary infections in patients in the control group and the ob-servation group was 30.9％(13/42)and 12.2％(5/41),respectively;the incidence of pulmonary infections in patients in the observation group was significantly lower than that in the control group(x2=4.298,P＜0.05).The incidence of anasto-motic fistula in patients in the observation group and the control group was 9.76％(4/42)and 21.43％(9/42),respectively;there was no statistically significant difference between the two groups(x2=2.140,P＞0.05).The postoperative hospital stay was significantly longer in the control group than in the observation group(P＜0.05),and the total hospitalization costs were significantly higher in the control group than in the observation group(P＜0.05).Conclusion Methylprednisolone can effec-tively reduce the levels of inflammatory markers and the incidence of postoperative pulmonary infections in esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy before surgery.It is a highly safe treatment thera-py without increasing the incidence of anastomotic fistula.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.