Study on the mechanism of Fangxia Dihuang Formula(FXDH) in treating breast cancer complicated with depression through the regulation of M1/M2 microglial polarization via the PERK/eIF2α axis. In addition to control group and 4T1 group, a mouse model of breast cancer complicated with depression was established using 4T1 cells combined with corticosterone. The mice were divided into model group, PERK/eIF2α signaling axis agonist(CCT020312, 2 mg·kg~(-1)·d~(-1)) group, CCT020312(2 mg·kg~(-1)·d~(-1)) + FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) + Capecitabine Tablets(CAP, 390 mg·kg~(-1)·d~(-1)) group, and Fluoxetine Hydrochloride Capsules(FXT, 2.6 mg·kg~(-1)·d~(-1)) + CAP(390 mg·kg~(-1)·d~(-1)) group, with continuous intervention for 21 d. Depression-like behaviors in mice were assessed through sugar preference test and open field test. Hematoxylin-eosin(HE) staining was used to evaluate the morphology of tumor and hippocampal DG region neurons. Nissl staining was employed to detect changes in Nissl bodies in the hippocampal CA3 region. Immunofluorescence was used to observe cluster of differentiation 86(CD86)/ionized calcium-binding adapter molecule 1(Iba-1) and cluster of differentiation 206(CD206)/Iba-1 in hippocampal tissue. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression of M1-type microglia [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] and M2-type [arginase-1(Arg-1), IL-10] in hippocampal tissue. Western blot was used to detect the protein expression of key factors in the PERK/eIF2α axis, including PERK, eIF2α, activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) in hippocampal tissue. The results showed that compared to model group/CCT020312 + FXDH group, FXDH group increased sugar preference index, total movement distance, central zone distance, and central zone entries; reduced tumor mass and volume; tumor cells were sparsely arranged, with a smaller nuclear-to-cytoplasmic ratio and reduced nuclear division figures, increased Nissl body count, and alleviated neuronal nuclear pyknosis; increased CD206-positive M2-type microglia expression, decreased CD86/Iba-1-positive M1-type microglia expression; reduced IL-6 and TNF-α mRNA expression, and increased Arg-1 and IL-10 mRNA expression; downregulated PERK, eIF2α, ATF4, and CHOP protein expression levels. The results indicate that the mechanism of FXDH in treating breast cancer complicated with depression may be related to inhibiting the activity of the PERK/eIF2α axis, reducing the proportion of M1-type microglia, increasing the proportion of M2-type microglia, thereby suppressing neuronal immune inflammation, improving depressive symptoms, and subsequently delaying the progression of breast cancer.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Microglia/cytology* ; Mice ; Depression/complications* ; eIF-2 Kinase/genetics* ; Humans ; Breast Neoplasms/psychology* ; Eukaryotic Initiation Factor-2/genetics* ; Mice, Inbred BALB C ; Signal Transduction/drug effects* ; Cell Line, Tumor

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

In 2005, the Chinese Invasive Fungal Infection Working Group published the first guidelines for the diagnosis and treatment of invasive fungal disease (IFD) in patients with hematological disorders and cancers, with the sixth revision released in 2020. Numerous advances in the fields of hematological oncology treatment and the diagnosis and management of IFD have significantly influenced the corresponding strategies. Therefore, the Chinese Invasive Fungal Infection Working Group has reviewed key research advances from 2020 to 2024 and released the seventh revision of the Chinese guidelines. Major revisions include: changes in the epidemiology of IFD; evaluation of novel diagnostic methods (especially PCR and metagenomic next-generation sequencing); updated recommendations on therapeutic drug monitoring and in vitro drug sensitivity test; management of breakthrough IFD; targeted therapy of Pneumocystis jiroveci pneumonia and cryptococcosis; and updated recommendation on the duration of antifungal therapy.
Humans ; Invasive Fungal Infections/drug therapy* ; Hematologic Diseases/complications* ; Antifungal Agents/therapeutic use* ; Neoplasms/complications* ; Hematologic Neoplasms/complications* ; Mycoses/therapy* ; China

OBJECTIVES: This study aimed to construct a risk prediction model for the occurrence of the demora-lization syndrome in patients with oral cancer and provide a scientific basis for the prevention of this syndrome in patients with oral cancer and the development of personalized care programs. METHODS: A total of 486 patients with oral cancer in West China Hospital of Stomatology of Sichuan University and Sun Yat-sen Memorial Hospital of Sun Yat-sen University from 2024 March to July were selected by convenience sampling. We integrated clinical data and evidence from previous studies to identify the key variables affecting the demoralization syndrome in patients with oral cancer. The 486 patients were divided into a training set and a validation set in an 8∶2 ratio. A clinical risk prediction model was established based on the individual data of 365 patients in the development cohort. Through least absolute shrinkage and selection operator (LASSO) regression, a moderate to severe risk prediction model of demoralization syndrome in oral cancer was constructed, and a clinical machine-learning nomogram was constructed. Bootstrap resampling was used for internal validation. The data of 121 patients in the validation cohort were externally validated. RESULTS: The incidence of the demoralization syndrome in patients with oral cancer was 405 cases (83.3%), of which 279 cases (57.4%) were mild, 176 cases (36.2%) were moderate, and 31 cases (6.4%) were severe. The core model, including patient education level, disease understanding, and MDASI-HN score, was used to predict the risk of outcome. Internal validation of the model yielded C statistic of 0.783 6 (95% CI: 0.78-0.87), beta of 0.843 4, and calibration intercept of -0.040 6. Through external validation, the validation set C statistic was 0.80 (95%CI: 0.71-0.87), beta was 0.80, and calibration intercept was -0.08. CONCLUSIONS Our risk prediction mo-del of the demoralization syndrome in patients with oral cancer performed robustly in validation cohorts of different nur-sing environments. The model has good correction and good discrimination and can be used as an evaluation and prediction item at admission.
Humans ; Mouth Neoplasms/complications* ; Male ; Female ; Nomograms ; Middle Aged ; Syndrome ; Aged ; Adult ; Risk Factors ; Risk Assessment ; Machine Learning

Hepatolenticular degeneration is a rare disease,and the number of cases of primary liver cancer occurring on the basis of liver cirrhosis caused by hepatolenticular degeneration is very small.This paper reports a case of hepatolenticular degeneration with primary liver cancer,and then reviews and summarizes current cases of this disease both domestically and internationally.
Humans ; Hepatolenticular Degeneration/complications* ; Liver Neoplasms/complications*

Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ²=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ²=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans ; Rectal Neoplasms/complications* ; Male ; Middle Aged ; Female ; Aged ; Contrast Media ; Ultrasonography ; Adult ; Magnetic Resonance Imaging ; Constriction, Pathologic/diagnostic imaging* ; Aged, 80 and over ; Intestinal Obstruction/etiology*

OBJECTIVE: To summarize the research progress of rodent models of secondary lymphedema (SL) and provide a reference for selecting appropriate animal models in SL research. METHODS: Recent literature on rodent SL models at home and abroad was comprehensively analyzed, summarizing model categories, development techniques, strengths, and weaknesses. RESULTS: Current research primarily utilizes rats and mice to establish SL models. The main model types include hind limb, forelimb, tail, and head/neck models. The hind limb model is the most frequently employed, typically requiring surgery combined with irradiation to induce stable chronic edema. Forelimb models primarily simulate upper limb lymphedema, but exhibit relatively rapid edema resolution. Tail models offer operational simplicity and are predominantly used for studying acute edema mechanisms and interventions; however, they demonstrate poor clinical relevance. Emerging head/neck models provide a valuable tool for investigating head and neck cancer-associated lymphedema. These models exhibit variations in lymphedema duration, degree of fibrosis, and edema incidences. CONCLUSION Existing models still fall short in faithfully replicating the chronicity, fibrosis, fat deposition, and complex microenvironment characteristic of human chronic lymphedema. Future research must integrate multidisciplinary approaches, optimize model construction strategies, and explore novel modeling approaches to more accurately mimic the human disease and advance SL prevention and treatment research.
Lymphedema/pathology* ; Animals ; Disease Models, Animal ; Rats ; Mice ; Humans ; Head and Neck Neoplasms/complications* ; Rodentia

OBJECTIVE: To compare the effectiveness of single-stage vascularized lymph node transfer (VLNT) combined with lymphaticovenular anastomosis (LVA) and liposuction (LS) (3L) versus LVA combined with LS (2L) for the treatment of moderate-to-late stage upper limb lymphedema following breast cancer surgery. METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with moderate-to-late stage upper limb lymphedema after breast cancer surgery, treated between June 2022 and June 2024, who met the selection criteria. Patients were divided into 3L group (n=7) and 2L group (n=9) based on the surgical approach. There was no significant difference (P>0.05) in baseline data between the groups, including age, body mass index, duration of edema, volume of liposuction, International Society of Lymphology (ISL) stage, preoperative affected limb volume, preoperative circumferences of the affected limb at 12 levels (from 4 cm distal to the wrist to 42 cm proximal to the wrist), preoperative Lymphoedema Quality of Life (LYMQoL) score, and frequency of cellulitis episodes. The 2L group underwent LS on the upper arm and proximal forearm and LVA on the middle and distal forearm. The 3L group received additional VLNT in the axilla, with the groin serving as the donor site. Outcomes were assessed included the change in affected limb volume at 12 months postoperatively, and comparisons of limb circumferences, LYMQoL score, and frequency of cellulitis episodes between preoperative and 12-month postoperative. Ultrasound evaluation was performed at 12 months in the 3L group to assess lymph node viability. RESULTS: Both groups were followed up 12-20 months, with an average of 15.13 months. There was no significant difference in the follow-up time between the groups (t=-1.115, P=0.284). All surgical incisions healed by first intention. No adverse events, such as flap infection or necrosis, occurred in the 3L group. At 12 months after operation, ultrasound confirmed good viability of the transferred lymph nodes in the 3L group. Palpation revealed significant improvement in skin fibrosis and improved skin softness in both groups. Affected limb volume significantly decreased in both groups postoperatively (P<0.05). The reduction in limb volume significantly greater in the 3L group compared to the 2L group (P<0.05). Circumferences at all 12 measured levels significantly decreased in both groups compared to preoperative values (P<0.05). The reduction in circumference at all 12 levels was better in the 3L group than in the 2L group, with significant differences observed at 7 levels (8, 12, 16, 30, 34, 38, and 42 cm) proximal to the wrist (P<0.05). Both groups showed significant improvement in the frequency of cellulitis episodes and LYMQoL scores postoperatively (P<0.05). While the improvement in LYMQoL scores at 12 months did not differ significantly between groups (P>0.05), the reduction in cellulitis episodes was significantly greater in the 3L group compared to the 2L group (P<0.05). CONCLUSION The combination of VLNT+LVA+LS provides more durable and comprehensive outcomes for moderate-to-late stage upper limb lymphedema after breast cancer surgery compared to LVA+LS, offering an improved therapeutic solution for patients.
Humans ; Female ; Lipectomy/methods* ; Retrospective Studies ; Anastomosis, Surgical/methods* ; Lymphedema/etiology* ; Middle Aged ; Upper Extremity/surgery* ; Breast Neoplasms/surgery* ; Lymph Nodes/blood supply* ; Adult ; Lymphatic Vessels/surgery* ; Iliac Artery/surgery* ; Postoperative Complications/surgery* ; Perforator Flap/blood supply* ; Treatment Outcome ; Mastectomy/adverse effects* ; Quality of Life ; Aged

OBJECTIVE: To optimize the perioperative management experiences for breast cancer patients undergoing direct-to-implant-based breast reconstruction, and provide reference for clinical practice. METHODS: A comprehensive review of recent domestic and international literature was conducted to systematically summarize the key points of perioperative management for direct-to-implant-based breast reconstruction, including preoperative health education, intraoperative strategies, and postoperative management measures, along with an introduction to the clinical experiences of West China Hospital of Sichuan University. RESULTS: Standardized perioperative management can effectively reduce the incidence of complications and achieve excellent cosmetic outcomes and quality of life after operation. Preoperative management includes proactive health education to alleviate patients' anxiety and improve treatment compliance, as well as comprehensive assessment by surgeons of the patient's physical condition and reconstructive expectations to select the most appropriate implant. Intraoperative management consists of strict aseptic technique, minimizing implant exposure, preserving blood supply to the nipple-areola complex (e.g., by using minimally invasive techniques or indocyanine green angiography, etc), and meticulous hemostasis. Postoperative management encompasses multimodal analgesia, individualized drain management (such as early removal or retaining a small amount of fluid to optimize contour), infection prevention and control (including topical and systemic antibiotics, ultrasound-guided minimally invasive drainage), guidance on rehabilitation exercises (early activity restriction followed by gradual recovery), and regular follow-up to evaluate aesthetic results and monitor for complications. CONCLUSION Establishing a standardized, multidisciplinary perioperative management framework markedly enhances surgical safety and patient satisfaction, thereby providing a replicable benchmark for direct-to-implant-based breast reconstruction across diverse clinical settings.
Humans ; Female ; Breast Neoplasms/surgery* ; China ; Perioperative Care/methods* ; Breast Implants ; Mammaplasty/methods* ; Breast Implantation/methods* ; Postoperative Complications/prevention & control* ; Quality of Life ; Mastectomy