Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels， but their effectiveness is limited. The mechanisms underlying its onset are complex， and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression， involving multiple pathways， including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 （TLR4/NLRP3）， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， brain-derived neurotrophic factor/tyrosine kinase receptor B （BDNF/TrkB）， cyclic AMP/protein kinase A/cAMP response element-binding protein （cAMP/PKA/CREB）， and others. Traditional Chinese medicine（TCM） is based on a holistic approach and the principle of treatment based on the differentiation of syndromes， regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems， involving liver Qi stagnation， heart spirit deficiency， kidney essence depletion， and spleen dysfunction. TCM compound treatments focus on soothing the liver， strengthening the spleen， calming the heart， and replenishing essence， with formulas such as Xiaoyaosan， Zishui Qinggan Yin， and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi， such as salidroside， ginsenoside Rb₁， astragaloside， and muscone. External TCM treatments， primarily acupuncture， aim to open the orifices and invigorate the spirit. Acupoints such as Baihui， Shenting， and Yintang are commonly used. Additionally， massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression， aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.

This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

Traditional Chinese medicine(TCM) processing is a specialized pharmaceutical technique with the primary objective of reducing the toxicity of medicinal substances. Euphorbia pekinensis, E. ebracteolata, and E. fischeriana, all belonging to Euphorbiaceae, are classified as drastic purgative herbs, traditionally used for eliminating retained water, reducing swelling, resolving toxicity, and dispersing masses. However, these herbs are also associated with adverse effects such as abdominal pain and diarrhea. Accordingly, they are commonly processed with vinegar, milk, or Terminalia chebula decoction to reduce the toxicity. This review summarizes the chemical constituents, pharmacological activities, historical evolution of processing methods, and detoxification mechanisms of the three toxic Euphorbia species. The primary toxic constituents are terpenoids. Specifically, E. ebracteolata and E. fischeriana are rich in diterpenoids, while E. pekinensis contains diterpenoids, triterpenoids, and sesquiterpenoids. Studies have shown that vinegar processing promotes structural transformations of diterpenoids, including ether bond hydrolysis, lactone ring opening, esterification, oxidation, and epoxide ring cleavage, thereby reducing the content and toxicity of these compounds. Milk processing facilitates the dissolution of toxic components into the residual liquid of excipients, leading to decreases in their concentrations in the final decoction pieces. Processing with T. chebula decoction raises the levels of tannin-derived phenolic acids, which antagonize the adverse effects of the intestine. These findings reveal a shared detoxification pattern among the three toxic herbs. Accordingly, this review proposes the concept of a shared detoxification mechanism for toxic herbs belonging to the same family or genus. That is, toxic herbs belonging to the same taxon often exhibit similar toxicological profiles and can undergo detoxification through the same processing methods, reflecting common underlying mechanisms. Investigating such shared mechanisms across multiple species of the same genus offers a promising research strategy. Ultimately, the research into processing-induced detoxification mechanisms provides both theoretical and practical support for ensuring the safety of toxic TCM.
Euphorbia/classification* ; Drugs, Chinese Herbal/metabolism* ; Humans ; Animals ; Inactivation, Metabolic ; Medicine, Chinese Traditional

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.