AIM:This study investigates the antidepressant mechanism of Jieyu-Anshen formula combined with selenium in chronic unpredictable mild stress(CUMS)mice through network pharmacology and animal experiments.METHODS:Potential drug targets were identified using the TCMSP,Genecards,and STRING databases.A protein-pro-tein interaction network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)enrichment analyses and molecular docking validation.Sixty male KM mice were divided into six groups:control,model,selenium,Jieyu Anshen formula,selenium+Jieyu Anshen formula,and fluoxetine.Depression-like behav-iors were assessed using the tail suspension test,forced swimming test,and elevated plus-maze test.Enzyme-linked immu-nosorbent assay(ELISA)was used to measure hippocampal levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,5-hydroxytryptamine(5-HT),and dopamine(DA).Histopathological changes in the hippocampus were ex-amined using hematoxylin and eosin(HE)staining.Additionally,protein expression levels of nuclear factor-κB p65(NF-κB p65),phospho-NF-κB-p65(p-NF-κB p65),prostaglandin-endoperoxide synthase 2(PTGS2),glutathione peroxidase 4(GPX4),and selenoprotein S(SelS)were detected through immunohistochemistry and Western blot.RESULTS:Jieyu-Anshen formula combined with selenium significantly improved depression-like behaviors in CUMS mice,reduced inflammatory cytokine(IL-6,TNF-α and IL-1β)levels,restored the levels of 5-HT and DA,and inhibited NF-κB signal-ing pathway activation.CONCLUSION:Jieyu Anshen formula combined with selenium significantly improved depres-sion-like behaviors in CUMS mice,potentially by improving hippocampal morphology,modulating the NF-κB signaling pathway,suppressing inflammatory factor expression,and enhancing hippocampal 5-TH and DA levels.

Radical resection of mid-and low-rectal cancer requires not only oncologic safety but also preservation of organs and postoperative bowel function.While a 1-2 cm distal resection margin has been largely accepted,the optimal length of the proximal margin remains highly controversial.Clinically,the"10-cm rule"derived from colon cancer is often referenced,yet its applicability to rectal cancer lacks consistent supporting evidence.Previous studies have shown that an excessively long proximal margin may increase anastomotic tension and lead to anastomotic leakage,whereas insufficient resection heightens the risk of positive margins and local recurrence.In addition,the extent of lymph node metastasis,vascular perfusion of the proximal bowel,radiation-induced injury after neoadjuvant chemoradiotherapy,and postoperative bowel function-particularly low anterior resection syndrome-are all important factors influencing the selection of the proximal margin.In recent years,the application of indocyanine green fluorescence imaging has provided new evidence for intraoperative assessment of bowel perfusion;for patients receiving neoadjuvant chemoradiotherapy,radiation injury presents a gradient pattern,and resecting approximately≥20 cm proximal to the tumor may reduce the incidence of anastomosis-related complications.Based on current literature,this review provides a systematic overview of the historical evolution,influencing factors,and clinical evidence regarding proximal resection margins in rectal cancer surgery,with the aim of informing individualized margin selection and optimizing surgical strategies.

In laparoscopic and robot-assisted ultra-low sphincter-saving surgeries for rectal cancer, preserving sexual function, preventing anastomotic leakage, anastomotic stricture, and low anterior resection syndrome (LARS) is critical to ensuring a good postoperative quality of life. The primary strategy for preventing postoperative sexual dysfunction is the meticulous preservation of the autonomic nerves, particularly the neurovascular bundles in the prostate area, guided by precise anatomical dissection. Partial preservation of the Denonvilliers fascia during total mesorectal excision (TME) not only helps protect the anterior mesorectum but also safeguards the neurovascular bundles. To prevent anastomotic leakage, it is essential to achieve clear oncologic margins, ensure a robust blood supply to both the proximal and distal margins, maintain a tension-free anastomosis, and avoid thermal or radiation injury whenever possible. In elderly patients with metabolic diseases, persistent descending mesocolon, or those undergoing neoadjuvant chemoradiotherapy, selective preservation of the left colic artery may be considered. Additionally, reinforcing the anastomosis with sutures at the 'dog-ear' site, closing the pelvic peritoneum, and placing a transanal tube for drainage are beneficial strategies. Early identification of anastomotic leakage and timely intervention to ensure drainage can prevent delayed leakage, strictures, and the structural sequelae of anastomotic failure. To minimize fecal dysfunction, selective exemption from radiotherapy may be beneficial for mid-to-high rectal cancer, while for low rectal cancer, reconstruction of J-pouch reservoirs, end-to-side anastomosis, and transverse coloplasty can help reduce the incidence of severe low anterior resection syndrome. Additionally, for low rectal cancer following neoadjuvant therapy, a selective rectum-preserving strategy that avoids major surgery can effectively prevent these complications.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

AIM:This study investigates the antidepressant mechanism of Jieyu-Anshen formula combined with selenium in chronic unpredictable mild stress(CUMS)mice through network pharmacology and animal experiments.METHODS:Potential drug targets were identified using the TCMSP,Genecards,and STRING databases.A protein-pro-tein interaction network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)enrichment analyses and molecular docking validation.Sixty male KM mice were divided into six groups:control,model,selenium,Jieyu Anshen formula,selenium+Jieyu Anshen formula,and fluoxetine.Depression-like behav-iors were assessed using the tail suspension test,forced swimming test,and elevated plus-maze test.Enzyme-linked immu-nosorbent assay(ELISA)was used to measure hippocampal levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,5-hydroxytryptamine(5-HT),and dopamine(DA).Histopathological changes in the hippocampus were ex-amined using hematoxylin and eosin(HE)staining.Additionally,protein expression levels of nuclear factor-κB p65(NF-κB p65),phospho-NF-κB-p65(p-NF-κB p65),prostaglandin-endoperoxide synthase 2(PTGS2),glutathione peroxidase 4(GPX4),and selenoprotein S(SelS)were detected through immunohistochemistry and Western blot.RESULTS:Jieyu-Anshen formula combined with selenium significantly improved depression-like behaviors in CUMS mice,reduced inflammatory cytokine(IL-6,TNF-α and IL-1β)levels,restored the levels of 5-HT and DA,and inhibited NF-κB signal-ing pathway activation.CONCLUSION:Jieyu Anshen formula combined with selenium significantly improved depres-sion-like behaviors in CUMS mice,potentially by improving hippocampal morphology,modulating the NF-κB signaling pathway,suppressing inflammatory factor expression,and enhancing hippocampal 5-TH and DA levels.

Radical resection of mid-and low-rectal cancer requires not only oncologic safety but also preservation of organs and postoperative bowel function.While a 1-2 cm distal resection margin has been largely accepted,the optimal length of the proximal margin remains highly controversial.Clinically,the"10-cm rule"derived from colon cancer is often referenced,yet its applicability to rectal cancer lacks consistent supporting evidence.Previous studies have shown that an excessively long proximal margin may increase anastomotic tension and lead to anastomotic leakage,whereas insufficient resection heightens the risk of positive margins and local recurrence.In addition,the extent of lymph node metastasis,vascular perfusion of the proximal bowel,radiation-induced injury after neoadjuvant chemoradiotherapy,and postoperative bowel function-particularly low anterior resection syndrome-are all important factors influencing the selection of the proximal margin.In recent years,the application of indocyanine green fluorescence imaging has provided new evidence for intraoperative assessment of bowel perfusion;for patients receiving neoadjuvant chemoradiotherapy,radiation injury presents a gradient pattern,and resecting approximately≥20 cm proximal to the tumor may reduce the incidence of anastomosis-related complications.Based on current literature,this review provides a systematic overview of the historical evolution,influencing factors,and clinical evidence regarding proximal resection margins in rectal cancer surgery,with the aim of informing individualized margin selection and optimizing surgical strategies.

In laparoscopic and robot-assisted ultra-low sphincter-saving surgeries for rectal cancer, preserving sexual function, preventing anastomotic leakage, anastomotic stricture, and low anterior resection syndrome (LARS) is critical to ensuring a good postoperative quality of life. The primary strategy for preventing postoperative sexual dysfunction is the meticulous preservation of the autonomic nerves, particularly the neurovascular bundles in the prostate area, guided by precise anatomical dissection. Partial preservation of the Denonvilliers fascia during total mesorectal excision (TME) not only helps protect the anterior mesorectum but also safeguards the neurovascular bundles. To prevent anastomotic leakage, it is essential to achieve clear oncologic margins, ensure a robust blood supply to both the proximal and distal margins, maintain a tension-free anastomosis, and avoid thermal or radiation injury whenever possible. In elderly patients with metabolic diseases, persistent descending mesocolon, or those undergoing neoadjuvant chemoradiotherapy, selective preservation of the left colic artery may be considered. Additionally, reinforcing the anastomosis with sutures at the 'dog-ear' site, closing the pelvic peritoneum, and placing a transanal tube for drainage are beneficial strategies. Early identification of anastomotic leakage and timely intervention to ensure drainage can prevent delayed leakage, strictures, and the structural sequelae of anastomotic failure. To minimize fecal dysfunction, selective exemption from radiotherapy may be beneficial for mid-to-high rectal cancer, while for low rectal cancer, reconstruction of J-pouch reservoirs, end-to-side anastomosis, and transverse coloplasty can help reduce the incidence of severe low anterior resection syndrome. Additionally, for low rectal cancer following neoadjuvant therapy, a selective rectum-preserving strategy that avoids major surgery can effectively prevent these complications.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective:To investigate the mechanism of Hongteng Decoction in inhibiting the adenomyosis (ADS) fibrosis by observing the effects on the key proteins of epithelial mesenchymal transformation (EMT), fibroblast-to-myofibroblast transformation (FMT) and Hippo pathway in uterine tissue of mice with ADS.Methods:ICR mice were divided into blank group, model group, Hongteng Decoction group, and verteporfin group according to random number table method, with 8 mice in each group. The day of birth of the mice was day 0, and from day 1, mice in model group, Hongteng Decoction group and verteporfin group were given 1 mg/kg tamoxifen solvent for gavage for 5 days. On the 42nd day after molding, HE staining verified that the molding was successful. Starting from the 43rd day, mice in the Hongteng Decoction group were given TCM solution of Hongteng Decoction 16.5 g/kg everyday, and intraperitoneally injected with 0.9%NaCl solution (100 μl/10 g) every 3 days. Mice in the verteporfin group were intraperitoneally injected with verteporfin solution of 100 mg/kg every 3 days, and intragastric with water of 100 μl/10 g everyday. Mice in blank group and model group were intragastric with constant volume of water daily and intraperitoneally injected with 0.9%NaCl solution every 3 days. The drugs were administered for 60 days. The fibrosis degree of mice in each group was evaluated by Masson staining. The expressions of E-cadherin, Vimentin, α-SMA, YAP and Snail in uterine tissue of mice in each group were detected by immunohistochemistry and Western blot.Results:Compared with the model group, the Masson staining expression in Hongteng Decoction group significantly decreased ( P<0.05). Immunohistochemical and Western blot analysis showed that the expression of E-cadherin in uterine tissue of mice in Hongteng Decoction group significantly increased ( P<0.05), while the expressions of Vimentin, α-SMA and YAP significantly decreased ( P<0.01, P<0.05) compared with the model group. Conclusion:Hongteng Decoction can inhibit the occurrence of EMT and FMT in ADS, thereby inhibiting fibrosis, and its mechanism is related to the regulation of Hipoo/YAP pathway.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.