AIM:To assess the influence of preoperative lacrimal passage probing and dilation on the therapeutic effectiveness of nasolacrimal silicone intubation in cases of incomplete primary acquired nasolacrimal duct obstruction(PANDO).METHODS: A retrospective case-control clinical study was conducted. The study included patients with incomplete PANDO who underwent nasolacrimal silicone intubation at the hospital between October 2022 and October 2024. Participants were categorized into two groups based on their receipt of nasolacrimal duct probing and dilation prior to intubation. Group A consisted of patients who had undergone one or more sessions of nasolacrimal duct probing and dilation before nasolacrimal silicone intubation, while Group B included patients who did not receive nasolacrimal duct probing and dilation before intubation. All patients had their nasolacrimal silicone tubes removed 3 mo postoperatively and were monitored for 6 mo following tube removal to evaluate surgical success rates.RESULTS: A total of 136 patients(152 eyes)completed the six-month follow-up period. The overall surgical success rate for both groups was 72.4%(110/152 eyes).Group A included 22 males and 36 females, mean age 58.09±11.07 y, and achieved a success rate of 82.8%(53/64 eyes), while Group B included 27 males and 51 females, mean age 59.35±8.84 y and attained a success rate of 64.8%(57/88 eyes). The difference in surgical success rates between the two groups was statistically significant(P=0.014). Furthermore, Group A achieved a complete success rate of 67.2%(43/64 eyes), compared to 47.7%(42/88 eyes)in Group B, with this difference also reaching statistical significance(P=0.017). No serious postoperative complications were observed in either group.CONCLUSION: Nasolacrimal silicone intubation is a safe and effective intervention for incomplete PANDO, with preoperative nasolacrimal duct probing and dilation potentially enhancing therapeutic outcomes.

Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

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*

Objective:To investigate the current state of death cognition among healthcare providers in hematology department and their attitudes toward hospice care for patients with hematologic malignancies.Methods:A cross-sectional investigation study was conducted. A total of 198 medical staff in hematology department of 4 teaching hospitals, including the First School of Clinical Medicine of Guangdong Medical University, Fujian Medical University Union Hospital, the Affiliated Hospital of Putian University and the First Affiliated Hospital of Gannan Medical University from March 2024 to June 2024 were selected as the investigation subjects. The general situation and background of medical staff in hematology department were investigated by using the "General Sociological Questionnaire". "Death Attitude Description Scale (Chinese version)" was used to investigate the status of death cognition among medical staff in hematology department. "Frommelt Attitudes Toward Care of the Dying Scale Form B (Chinese version)" was used to investigate the hospice care attitude of medical staff in hematology department. The survey results of doctors and nurses were compared.Results:There were 105 doctors and 93 nurses in hematology department included in this study. A total of 198 qualified "General Sociology Questionnaires" were collected. After excluding 6 unqualified questionnaires, 192 copies of "Death Attitude Description Scale (Chinese version)" and "Frommelt Attitudes Toward Care of the Dying Scale Form B (Chinese version)" were collected. There were statistically significant differences in gender, educational background, political status and experience of taking care of terminally ill patients between doctors and nurses (all P < 0.05). The scores of approaching acceptance, neutral acceptance, death escape, death fear and flight acceptance were (4.35±0.37), (4.03±0.51), (2.98±0.62), (2.54±0.29) and (2.19±0.42) points, respectively in the doctor group; the corresponding scores were (3.12±0.41), (3.89±0.46), (2.66±0.63), (2.81±0.57) and (2.37±0.65) points, respectively in the nurse group, and the differences between the 2 groups were statistically significant (all P < 0.05). The total score of hospice care attitude of doctors in hematology department was (108±15) points, and that of nurses was (116±13) points, and the difference was statistically significant ( t = -3.61, P < 0.001). The hospice care attitude of doctors and nurses towards patients with hematologic malignancies is generally between positive and neutral. The nurse group showed more recognition of the positive role of the patient's family members in the process of hospice care, and the doctor group showed more recognition of the promoting role of medical staff in hospice care. There were statistically significant differences in hospice care attitude scores of medical staff in hematology department to patients with different occupational background, gender, age, place of residence, family discussion about death, whether the only child, whether they had the experience of taking care of terminally ill patients, and whether they suffered from serious illness and religious belief (all P < 0.05). Conclusions:The death cognition of medical staff in hematology department is neutral, and they show a certain sense of hospice care.

Objective To systematically evaluate the differences in clinicopathologic features and prog-nosis of colorectal cancer(CRC)between youth and middle-aged and elderly people.Methods The relevant literatures in Chinese and English databases before June 2024 were retrieved.The Stata 18 and RevMan5.3 softwares were used to perform the heterogeneity and sensitivity analyses as well as publication bias tests for the relevant outcome indicators.Results A total of 17 case-control studies were included,including a total of 6 817 patients with pathologically diagnosed CRC,among them 1 939 cases in the young group and 4 878 cases in the middle-aged and elderly group.The results of meta analysis showed that the proportion of family histo-ry in the young adult group(OR=3.09,95%CI:2.33-4.09),misdiagnosis rate(OR=4.40,95%CI:3.30-5.86),proportion of poorly differentiated carcinomas(OR=3.57,95%CI:2.73-4.67),proportion of mucin-ous adenocarcinomas and imprinted cell carcinomas(OR=3.41,95%CI:2.79-4.18),and proportion of TNM stage at diagnosis(stage Ⅲ-Ⅳ,OR=1.71,95%CI:1.44-2.02),incidence rate of lymph node metas-tasis(OR=1.92,95%CI:1.61-2.28),incidence rate of distant metastasis(OR=2.09,95%CI:1.53-2.86)were higher than those in the middle-aged and elderly group(all P<0.05);the CEA-positive rate at diagnosis(OR=0.68,95%CI:0.57-0.80)and 5-year survival rate(OR=0.24,95%CI:0.16-0.36)in the young group were lower than those in the middle-aged and elderly group(all P<0.05).The difference in the tumor diameter size(OR=1.32,95%CI:0.98-1.77)between the two groups was not statistically significant(P=0.07).Conclusion Compared with middle-aged and elderly CRC,young patients with CRC has a closer famil-ial correlation,may be more easily misdiagnosed clinically,its malignant degree would be higher,and the TNM stage in diagnosis is relatively late;in clinic the young population with CRC high risk could be appropriately relaxed in the age limit for screening.

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a chronic liver condition intricately linked to metabolic abnormalities such as obesity,type 2 diabetes,dyslipidemia,and hypertension.The global prevalence of MASLD continues to rise,posing a significant public health challenge.The pathogenesis of MASLD is multifactorial,with the"multiple-hit"hypothesis suggesting that hepatic lipid accumulation,insulin resistance,oxidative stress,gut microbiota dysbiosis,and genetic factors collectively drive disease progression.Currently,clinical management primarily relies on lifestyle interventions;however,there is a lack of targeted pharmacological interventions,and there is an urgent need to investigate novel adjunctive therapeutic strategies.In recent years,probiotics have demonstrated potential value in MASLD treatment due to their capacity to modulate gut microbiota,enhance insulin sensitivity,and reduce liver inflammation.This review systematically examines the pathogenesis of MASLD and the limitations of existing therapeutic approaches,synthesizing the latest evidence of probiotics-assisted therapy for MASLD from the perspectives of animal studies and clinical trials.By analyzing the target mechanisms and molecular pathways of different strains(e.g.,Bifidobacterium,Lactobacillus),this review explores the translational potential of probiotics in MASLD treatment,aiming to provide a theoretical foundation and future research directions.