Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

ObjectiveTo analyze the impact of diabetes-related deaths on the probability of premature mortality and life expectancy in Minhang District of Shanghai from 2004 to 2023, and to provide reference data for the optimization of targeted prevention and control strategies. MethodsAll death cases involving diabetes among the registered residents of Minhang District from 2004 to 2023 were collected. The probability of premature mortality and life expectancy was computed using the abridged life table method. The average annual percent change (AAPC) was calculated with Joinpoint 4.9.0.0. The Arriaga decomposition method was employed for statistical analyses of the influence of cause-specific and age-specific mortality related to diabetes on life expectancy. ResultsThe total number of diabetes-related mortality, crude mortality, and standardized mortality for both males and females in Minhang District from 2004 to 2023 exhibited an increasing trend (P<0.001). The primary causes of death among diabetes-related cases were cardiovascular disease (37.68%), diabetes mellitus (31.95%), and malignant tumor (17.80%). From 2004 to 2023, probability of premature mortality to diabetes-related diseases demonstrated a rising trend (P<0.001), contrasting with the declining trend observed in the overall population (P=0.001). Males showed a significant upward trajectory (P<0.001), while females displayed a stable pattern. Among the diseases exerting considerable influence, cardiovascular disease and malignant tumor revealed a marked increase over time (P<0.001), whereas diabetes mellitus maintained a stable trend; both factors negatively impacted the reduction in probability of premature mortality. From 2004 to 2023, diabetes-related mortality reduced life expectancy among residents by an average of 1.22 years (-49.89%), indicating a negative impact; the reduction was 1.41 years in males and 0.90 years in females. The age groups exhibiting greater negative contributions differed by genders, namely males aged 50‒54 years and females aged 70‒74 years. Cardiovascular disease, diabetes mellitus, and malignant tumor contributed significantly to this decline (-0.46 years, -0.42 years, -0.20 years, respectively), with male experiencing higher negative contributions than females. ConclusionIn Minhang District, the rising mortality associated with diabetes-related diseases negatively impact both the reduction of the probability of premature mortality and the increase in life expectancy. This trend is primarily attributed to the rapid escalation of mortality and younger age demographic of male residents, which warrants significant attention. It is recommended that, based on the enhancement of case management, efforts should be directed towards the targeted prevention and control of risk factors and high-risk populations.

Objective To explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis.Methods Analysis was conducted on data from genome-wide association studies(GWASs)on Omega-3 fatty acids and breast cancer.The selected instrumental variables(IVs)comprised genetic loci associated with Omega-3 fatty acids.Various Mendelian randomization analysis methods,including inverse-variance weighted(IVW)method,MR-Egger regression analysis,weighted median,simple models,and weighted models,were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer.Results A total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs.The analysis methods,including IVW method,revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer(P>0.05).Analysis methods,such as MR-Egger regression analysis,did not detect significant gene-level pleiotropy(P=0.319),which indicates the high sensitivity and robustness of analysis results.Conclusion The findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.

Objective To explore the effect of miR-1-3p on the malignant biological behavior of human esophageal squamous cell carcinoma cells and the potential mechanisms.Methods The Gene Expression Omnibus(GEO)database was analyzed to screen differentially expressed miRNAs in esophageal squamous cell carcinoma(ESCC).qRT-PCR was used to detect the expression of miR-1-3p in human ESCC cell lines(KYSE30,KYSE150,KYSE410,KYSE510,and Eca109)and normal esophageal epithelial cell line HET-1A.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of miR-1-3p on the proliferation,migration,invasion,and apoptosis of ESCC cells.Bioinformatics tool was used to predict the target genes of miR-1-3p.A Kaplan-Meier survival curve was drawn to analyze the correlation between STC2 expression and overall survival of patients in the ESCC cohort of the TCGA database.Fluorescence in situ hybridization was performed to verify the subcellular location of miR-1-3p in ESCC cells,and dual-luciferase reporter gene assay was performed to validate the regulation of miR-1-3p on stanniocalcin 2(STC2).RNA immunoprecipitation assays were used to detect the binding of miR-1-3p and STC2.Western blot assay was performed to determine the effect of miR-1-3p on the expression of STC2 and endoplasmic reticulum stress pathway-related proteins,including p-PERK,p-eIF2α,and ATF4.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of STC2 overexpression and knockdown on the proliferation,migration,invasion,and apoptosis of ESCC cells.Results The expression of miR-1-3p was lower in ESCC cell lines than in HET-1A cells(all P<0.05).The transfection of miR-1-3p mimic decreased the proliferation,invasion,and migration of ESCC cells(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.001).Bioinformatics tool showed that STC2 was a target gene of miR-1-3p.The expression of STC2 in ESCC tissues was higher than that in normal esophageal epithelial tissues in the ESCC cohort of TCGA database and was negatively correlated with prognosis(all P<0.05).miR-1-3p was located in the cytoplasm and can directly bind to STC2 mRNA.The transfection of miR-1-3p mimic downregulated the expression of STC2,p-PERK,p-eIF2α,and ATF4(all P<0.05).The overexpression of STC2 promoted the proliferation,invasion,and migration(all P<0.05)and inhibited the apoptosis of ESCC cells(all P<0.05).Knockdown of STC2 inhibited the proliferation,invasion,and migration(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.05).Conclusion miR-1-3p inhibits the malignant biological behavior and promotes the apoptosis of esophageal squamous cell carcinoma cells by regulating STC2 possibly by suppressing the endoplasmic reticulum stress.

Objective:The aim of this study was to explore whether hydroxysafflor yellow A (HSYA) combined with hyaluronidase (HAase) can enhance the therapeutic effect of arterial embolism caused by hyaluronic acid (HA) .Methods:Thirty-two white male rabbits were randomly divided into four groups, with 8 rabbits in each group, of which group A, B and C were experimental groups and group D was group control. An axial rectangular composite tissue flap sized 2.0 cm × 5.0 cm, with 1.0 cm pedicle width, and 4.0 cm from the root, was designed with the central auricular artery as the long axis on the dorsal side of the ear. The depth of incision reached the ventral perichondrium of the ear, and the flap was sutured continuously in situ and divided into three equal parts (area Ⅰ, Ⅱ, Ⅲ) from the proximal area to the distal area. The proximal end 1 cm to the flap and the central artery was the intersection point, into which 50 μl HA was injected, by which the model of HA arterial embolism was established. Each group was treated after 60 min. Group A: 20 ml solution HSYA was injected slowly into the thigh saphenous vein (the dosage of HSYA is calculated at 10 mg/kg) . Group B: 0.5 ml solution HAase was injected into the central auricular artery (400 U/ml) . Group C: 0.5 ml solution HAase with the same dosage of group B was injected into the central auricular artery and 20 ml solution HSYA with the same dosage of group A was injected slowly into the thigh saphenous vein. Group D and other parts of group A and B were injected with the same dosage of normal saline (NS) . The thigh saphenous veins of all groups were injected with the same dosage of solution once a day for 14 days. Flaps were observed immediately, 1, 7 and 14 days after establishment of hyaluronic acid arterial embolism models of tissue flaps, and dorsal and backlight auricular photographs were taken. On the postoperative 14th day, percentages of survival areas of the flaps were calculated, and samples were taken from areas II of tissue flaps, which were stained by hematoxylin-eosin (HE) and Masson, and were detected the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) . The measurement data conformed to normal distribution was represented as Mean ± SD. Single factor analysis of variance (ANOVA) was used to compare the differences among groups, and head-to-head comparison by LSD test. P <0.05 was considered statistically significant. Results:Tissue flaps of all groups were pale immediately after operation. On the first day after operation, the dark ischemic area appeared at the distal end of each group. On the postoperative 7th day, the ischemic area of each group was necrotic and blackened to varying degrees, and the non-necrotic area swelled obviously. On the postoperative 14th day, the ischemic area of each group was further necrotic, blackened, curled and the boundary was clear. Group C was the best, group D was the worst, and both group A and B were between the two. The swelling of non-necrotic areas in group A and C were basically reduced. HE staining showed that numerous thrombi and inflammatory cells infiltration were formed in group D, and group B was behind it, and thrombi were rare in group A and C. Masson staining showed that collagen fibers were arranged regularly in group C, and abundant collagen fibers were disintegrated and disordered in group D, and both group A and B were between the two. The percentages of survival areas of the flaps in group A, B, C and D were as follows: (69.87 ± 5.04) %, (85.03 ± 6.58) %, (93.93 ± 4.25) % and (49.22±9.64) %. There were statistical differences in pairwise comparison between groups (all P <0.05) . SOD activity of group A, B, C and D were as follows: (49.83±8.08) , (36.65±5.49) , (55.61±7.93) and (22.45 ± 5.47) U/mg prot. Except that group A vs. C, there were statistical differences between groups (all P <0.05) . MDA content of group A, B, C and D were as follows: (0.77±0.17) , (1.03±0.16) , (0.68±0.12) , and (0.41±0.09) nmol/mg prot. Except that group A vs. C, there were statistical differences between groups (all P <0.05) . Conclusions:Under the condition of animal experiment, compared with HAase, HSYA combined with HAase can significantly enhance the therapeutic effect of HA arterial embolism and increase the proportion of survival area of tissue flap.

Objective:To explore the therapeutic effect of hydroxysafflor yellow A (HSYA) combined with hyaluronidase (HAase) for arterial embolism caused by hyaluronic acid (HA).Methods:Thirty-two white male rabbits were randomly divided into four groups, with 8 rabbits in each group. Groups A, B and C were experimental groups, while group D served as the control group. An axial rectangular composite tissue flap sized 2.0 cm × 5.0 cm, with a pedicle width of 1.0 cm, and located 4.0 cm from the root, was designed with the central auricular artery as the long axis on the dorsal side of the ear. The incision depth reached the ventral perichondrium of the ear, and the flap was sutured continuously in place and divided into three equal parts (areas Ⅰ, Ⅱ, Ⅲ) from the proximal to the distal area. The proximal end, located 1 cm from the flap, and the central artery was the intersection point, where 50 μl of HA was injected to establish the model of HA arterial embolism. Each group was treated after 60 minutes. Group A: 20 ml of HSYA solution was slowly injected into the saphenous vein of the thigh (the dosage of HSYA was calculated at 10 mg/kg). Group B: 0.5 ml of HAase solution was injected into the central auricular artery (400 U/ml). Group C: 0.5 ml of HAase solution with the same dosage as in group B was injected into the central auricular artery, while 20 ml of HSYA solution with the same dosage as in group A was slowly injected into the saphenous vein. Group D and other parts of groups A and B were injected with the same dosage of normal saline (NS). The thigh saphenous veins of all groups were injected with the same dosage of solution once daily for 14 days. Flaps were observed immediately, 1, 7 and 14 days after establishing hyaluronic acid arterial embolism models of tissue flaps. Dorsal and backlight auricular photographs were taken. On the 14th day postoperatively, the survival areas of the flaps were calculated. Samples were taken from areas Ⅱof tissue flaps, stained with hematoxylin-eosin (HE) and Masson, to detected the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). The measurement data that conformed to a normal distribution was represented as Mean ± SD. Single-factor analysis of variance (ANOVA) was used to compare the differences among groups, followed by head-to-head comparison using the LSD test. P<0.05 was considered statistically significant. Results:Tissue flaps from all groups appeared pale immediately after the operation. On the first day after the operation, a dark ischemic area appeared at the distal end of each group. On the 7th day postoperatively, the ischemic area of each group showed varying degrees of necrosis and blackening, while the non-necrotic area exhibited significant swelling. On the 14th day post-operation, the ischemic area in each group showed further necrosis, blackening, and curling, with clear boundaries. Group C was the best, group D was the worst, and both group A and B were in between the two. The swelling of non-necrotic areas in groups A and C was reduced. HE staining revealed numerous thrombi and infiltration of inflammatory cells in group D, with group B following closely behind. Thrombi were rare in groups A and C. Masson staining showed that collagen fibers were organized regularly in group C, while abundant collagen fibers were disintegrated and disordered in group D. Groups A and B exhibited characteristics that fell between the other two groups. The percentages of survival areas of the flaps in groups A, B, C and D were as follows: (69.87±5.04)%, (85.03±6.58)%, (93.93±4.25)% and (49.22±9.64)%. There were statistical differences in pairwise comparisons between groups (all P<0.05). SOD activity of groups A, B, C, and D were as follows: (49.83±8.08), (36.65±5.49), (55.61±7.93) and (22.45±5.47) U/mg prot. Except for the group A vs. C, there were statistical differences between the groups (all P<0.01). The MDA content of groups A, B, C and D were as follows: (0.77±0.17), (1.03±0.16), (0.68±0.12), and (0.41±0.09) nmol/mg prot. Except that group A vs. C, there were statistical differences between groups (all P<0.01). Conclusion:In animal experiments, it was found that compared to HAase alone, the combination of HSYA with HAase significantly improves the therapeutic outcomes of HA arterial embolism and increases the proportion of tissue flap survival area.

Objectives:To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer.Methods:Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m 2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results:All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period.Conclusions:LDER is safe and effective for the treatment of low rectal cancer.