ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To compare the oncologic safety, surgical efficacy, and aesthetic outcomes between conventional breast-conserving surgery and axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery in early breast cancer patients. Methods A retrospective analysis of clinical data from 62 female patients with early breast cancer was performed. Patients were divided into two groups on the basis of surgical method: the conventional group (37 cases) and the endoscopic group (25 cases).The clinical baseline data, surgical results, and postoperative effects of the two groups were compared. Results According to the clinical baseline data, the endoscopic group had a greater maximum tumor diameter and a greater tumor-to-breast volume ratio due to expanded indications for breast-conserving surgery (P<0.001), whereas the other data revealed no statistically significant difference between the two groups (P>0.05). Compared with those in the conventional group, the total incision length in the endoscopic group was shorter [3.40(3.15, 3.60) cm vs. 7.30 (6.50, 7.60) cm, P<0.001], the postoperative drainage volume was lower (206.20±35.11 ml vs. 223.95±26.17 ml, P=0.026), but the operative time was longer (254.92±22.67 min vs. 146.78±13.01 min, P<0.001). The incision margin positive rate was 0% (0/25) in the endoscopic group, which was significantly lower than the 10.8% (4/37) in the conventional group (P=0.141). The endoscopic group had a lower incidence of complications (4% vs. 27%, P=0.047) and superior JBCS aesthetic scores at the 6-month follow-up (76% vs. 43.2%, P=0.006). Conclusion Axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery is not inferior to conventional procedures in terms of oncologic safety (margin-negative rate) and offers advantages in terms of scar concealment, fewer complications, and better aesthetic outcomes, especially suitable for early breast cancer patients with small-to-medium breast volumes, tumors located in the outer quadrants and mastectomy ratios of >20%.