Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Objective: To understand the incidence risk and risk factors of tuberculosis (TB) among middle school students in Chongqing, so as to provide a basis for formulating TB prevention and control strategies. Methods: From September to December 2022, 32 181 middle school students were selected as the study cohort from 15 administrative districts in Chongqing by using the stratified cluster random sampling method. All cohort members were screened with the tuberculin skin test (TST), and relevant information was collected from January 1, 2023 to December 31, 2024. On the basis of active screening, the follow up data of the participants were compared with the National Tuberculosis Management Information System to obtain the incidence status of the study subjects. The Log rank test was used to compare the TB incidence rates among students with different characteristics, and a Cox proportional hazards model was established to analyze the incidence risk and risk factors of TB. Results: The TST screening rate of the cohort members was 93.0%. During the 2 year follow up period, a total of 36 TB cases occurred, with a cumulative incidence rate of 111.87/100 000 and an incidence density of 55.95/100 000. Among them, the cumulative incidence rate of students from public schools (170.44/ 100 000 ) was higher than that of students from private schools (41.16/100 000), the cumulative incidence rate of students in schools located in high epidemic areas (153.95/100 000) was higher than that in medium epidemic areas (69.00/100 000), and the difference was statistically significant ( χ 2=11.49, 4.73, both P <0.05). The Log-rank test for different TST results showed that the difference in TB comulative incidence rate between students with strongly positive TST results (216.55/ 100 000 ) and those with negative TST results (81.40/100 000) was statistically significant ( χ 2=5.85, P <0.05). Univariate analysis using the Cox proportional hazards model revealed that the risk of TB was lower in students from private schools ( HR=0.25, 95% CI = 0.10-0.59) and students in medium epidemic areas ( HR=0.46, 95%CI =0.23-0.94); whereas the risk of TB was increased in students with strongly positive TST results ( HR=1.39, 95%CI =1.05-1.84) (all P <0.05). Multivariate Cox regression analysis showed that the risk of TB in students from private schools was lower than that of students from public schools ( HR=0.23, 95%CI=0.08-0.62, P <0.05). Conclusions The annual average incidence rate of TB among middle school students in Chongqing is at a relatively high level. It is necessary to strengthen the management and intervention for student groups, including those in public schools, those in schools located in high epidemic areas, and those with strongly positive TST results, so as to reduce the incidence rate of TB.

OBJECTIVE: To observe the clinical efficacy of different acupuncture methods in the treatment of ankylosing spondylitis (AS) at different stages. METHODS: Thirty-two patients with AS were treated with acupuncture at ashi points (tendon focus), triple acupuncture method was used in the acute phase, accompanied needling method was used in the remission phase, once a day, 5 times a week for 4 weeks. The Bath ankylosing spondylitis disease activity index (BASDAI) score, Bath ankylosing spondylitis functional index (BASFI) score and TCM symptom grade quantitative standard score before and after treatment were observed, and the efficacy was evaluated. RESULTS: After treatment, the BASDAI score, BASFI score and TCM symptom grade quantitative standard score were reduced compared with those before treatment (P<0.01), the effective rate was 96.9% (31/32). CONCLUSION Different acupuncture methods in the treatment of AS at different stages could improve signs and symptoms, such as pain, activity limitation and morning stiffness.
Humans ; Spondylitis, Ankylosing/physiopathology* ; Acupuncture Therapy/methods* ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Acupuncture Points ; Treatment Outcome

Based on the pathogenesis of erectile dysfunction (ED) from the meridian-zangfu relationship and the "brain-heart-kidney-essence chamber" axis, it proposes that dysfunction of the "brain-heart-kidney-essence chamber" axis is closely related to the occurrence of ED. Among these, brain-heart disharmony is the key pathogenic factor, kidney deficiency and essence depletion constitute an important basis, and essence chamber stasis is a critical mechanism. The treatment approach emphasizes harmonizing the brain and heart, regulating the mind, tonifying the kidney and replenishing qi, unblocking qi and blood to harmonize the essence chamber. The primary acupoints include Baihui (GV20)-Neiguan (PC6)-Shenmen (HT7), Taixi (KI3)-Guanyuan (CV4)-Sanyinjiao (SP6), and Zhongji (CV3)-Dahe (KI12)-Gongsun (SP4), with additional acupoints selected based on syndrome differentiation. This approach aims to restore the clarity of the brain and heart, replenish kidney qi, and unblock the essence chamber, thereby facilitating the restoration of normal functions of the brain, heart, kidney, and essence chamber, and alleviating ED symptoms and improving overall clinical efficacy.
Humans ; Male ; Meridians ; Erectile Dysfunction/physiopathology* ; Kidney/physiopathology* ; Brain/physiopathology* ; Acupuncture Therapy ; Acupuncture Points ; Heart/physiopathology*

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

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Objective:To establish a determination method of liquid chromatography-tandem mass spectrometry(LC-MS/MS)for VK2 in serum,and to investigate the relationship between postmenopausal osteoporotic women and healthy women in MK-4 and MK-7 of VK2 supplements.Methods:Serum samples were collected from 126 women who admitted to Beijing Jishuitan Hospital of Capital Medical University.The women with postmenopausal osteoporosis were included in the osteoporosis group(72 cases),and the subjects without osteoporosis who received examination were included in the healthy control group(54 cases).LC-MS/MS was used to determine the levels of MK-4 and MK-7 in VK2,and the accuracy and precision were calculated.The differences in MK-4 and MK-7 between postmenopausal osteoporotic women and women who did not suffer osteoporosis were compared and analyzed.Results:In the chromatograms of standards and serum specimens detected by HPLC-MS/MS,the recoveries of different concentrations were between 101%-107%,and the precisions all met the requirements of quantitative detection(<20%).The average level of serum MK-7 of osteoporosis group was(0.48±0.12)ng/mL,which was significantly higher than(0.24±0.10)ng/ml of the healthy control group,and the difference was significant(t=11.917,P<0.05).The average level(0.07±0.02)ng/mL of serum MK-4 of the healthy control group was significantly higher than(0.04±0.01)ng/mL of osteoporosis group,and the difference was significant(t=-11.021,P<0.05).Conclusion:The LC-MS/MS method of determining VK2 that is established by this study has a series of advantages,such low cost,strong selectivity and high sensitivity,which is suitable to conventional detection for serum MK-4 and MK-7 levels,and it can simultaneously detect multiple-analytes with different concentration in serum,while it would not affect the levels of any other proteins.

Objective:To evaluate the clinical value and safety of an intraperitoneal chemotherapy port technique in patients with gastric cancer and peritoneal metastases undergoing intraperitoneal chemotherapy.Methods:This was a retrospective, descriptive case analysis. From November 2022 to October 2024, patients diagnosed with gastric cancer and peritoneal metastases at Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine with an expected survival >3 months, underwent laparoscopic exploration combined with implantation of an intraperitoneal chemotherapy port [PORT-A-CATH II system (Model 21-4055-24)] implantation. The procedure was as follows: (1) after laparoscopic exploration, a 4-cm skin incision was made at a predetermined site and a subcutaneous pocket created by dissecting to the muscle fascia and removing subcutaneous fat as needed to position the port septum 0.5-1.0 cm from the skin surface; (2) under direct laparoscopic visualization, the abdominal cavity was punctured and a guidewire inserted, followed by an 8.5 Fr sheath, through which a catheter with three trimmed side holes was placed after removal of the sheath; (3) the catheter length in the abdominal cavity was adjusted to 25–30 cm and the catheter trimmed, and connected to the port base, ensuring it extended beyond the connector's visible hole; (4) the whole port was placed within the subcutaneous pocket, and non-absorbable sutures used to create a double purse-string suture at the catheter's abdominal entry, forming an anti-reflux ring; (5) non-absorbable sutures were used to securely fix the port to the fascia through its four base holes and the exposed catheter segments on the fascia sutured and buried; (6) patency was confirmed by injecting saline and followed by intermittent skin closure provided there was no bleeding; and (7) the catheter tip was positioned in the pelvic cavity under laparoscopic guidance. Postoperatively, the patients underwent normothermic intraperitoneal and systemic treatment. The port infusion protocol involved disinfecting the skin (>10 cm diameter) around the port, confirming the puncture site, inserting a Huber needle vertically at 90° to the port base, infusing 100 mL saline to ensure patency, followed by continuous infusion of 1000 mL paclitaxel solution, and sealing with 20 mL saline before removing the needle. No saline flushing was required between chemotherapy infusions. The primary outcomes were the incidence and management of complications post-port implantation.Results:The study cohort comprised 225 patients with gastric cancer and peritoneal metastases. Using standardized port implantation and postoperative puncture procedures, the complication rate during follow-up was 14.2% (32/225), including effusion in 14 patients (6.2%), port infection in 10 (4.4%), incision dehiscence in four (1.8%), port inversion in two (0.9%), hematoma in one (0.4%), and catheter rupture in one (0.4%). Seventy-five percent (24/32) of patients with complications recovered and continued using the port after conservative treatments (e. g., aspiration of effusions, antibiotic therapy, incision management), whereas the remaining 25.0% (8/32) with complications required surgical removal of the port because the treatment was ineffective. The presence of preoperative ascites ( P=0.019) and peritoneal cancer index score>15 ( P=0.038) were significantly associated with development of complications. Conclusions:Our standardized procedure for intraperitoneal chemotherapy port implantation is safe and feasible for patients with gastric cancer and peritoneal metastases, having a low overall complication rate. Most complications can be successfully managed with conservative treatment, the device thus providing reliable support for intraperitoneal chemotherapy.