ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

ObjectiveTo investigate the effect of Naoqingtong decoction （NQT） on the kidney damage and the inflammatory factors NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in spontaneously hypertensive rats （SHRs）. MethodsTwenty-four SHRs were randomized into a model group， a low-dose （12.9 g·kg^-1·d^-1） NQT （NQT-L） group， a high-dose （25.8 g·kg^-1·d^-1） NQT group （NQT-H）， and a captopril （CTP， 20 mg·kg^-1·d^-1） group， with 6 rats in each group. In addition， 6 homozygous male Wistar-Kyoto rats were used as the control group. The control and model groups were administrated with the same amount of normal saline by gavage for 8 weeks. General behaviors of rats were observed during the intervention period， and the blood pressure was measured periodically. At the end of intervention， the body mass was weighed， and both kidneys were collected and weighed for the calculation of the renal index. Hematoxylin-eosin staining was performed to observe the pathological changes in the kidney tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue. ResultsDuring the experiment period， the control group had normal mental status， food intake， and activity， while the model group showed thinning of hair， loss of luster， reduced activity， loss of appetite， fecal adhesion， and irritability， and some of the skin had scratches or blood scabs. The above symptoms were alleviated to different degrees after 8 weeks of NQT administration. An intelligent non-invasive sphygmomanometer was used to measure the tail artery pressure of rats， which showed that the systolic and diastolic blood pressure of rats in the model group was higher than that in the control group （P<0.01）. Compared with the model group， drug interventions lowered the systolic and diastolic blood pressure （P<0.05， P<0.01）. Compared with the control group， the model group showed severe pathological damage in the kidney tissue， which was alleviated in each drug intervention group. Compared with the control group， the model group showed up-regulated expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue （P<0.05， P<0.01）. Compared with the model group， the drug intervention groups showed down-regulated expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue （P<0.05， P<0.01）. ConclusionNQT can lower the blood pressure in SHRs by inhibiting the activation of NLRP3 inflammasomes， suppressing renal inflammation， and ameliorating hypertensive kidney damage.

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Objective To construct an evaluation index system for rational drug use management of key monitoring drugs,and to provide references for medical institutions.Methods The preliminary index framework was formed by researching the policies and regulations,management norms,and guiding principles related to key monitoring drugs.Two rounds of Delphi questionnaire survey were conducted with 26 experts to improve and optimize the index system.The weights of the indicators were obtained by constructing the judgment matrix by analytic hierarchy process(AHP).Results The recovery rates of the two rounds of questionnaire were both 100％,and the authority coefficient was 0.87.The key monitoring drug rational use management evaluation index system was finally constructed to include three primary indicators[ex-ante management(0.253 6),in-process management(0.503 1),and ex-post management(0.243 2)],15 secondary indicators[including prescription review(0.302 6),formulate rational drug use norms(0.133 1),supernormal early warning management(0.103 2)],and 62 tertiary indicators[inclu-ding formulate strict prescription review rules(0.152 5),pharmacists prescription intervention strength(0.085 7)and effective-ness management(0.052 5)].and the index judgment matrix passed the consistency test.Conclusion The evaluation index system for the rational drug use management of key monitoring drugs constructed can satisfy the closed loop of the supervision and management process,achieve the prior reminder,monitoring,and post-supervision,and provide references for medical institutions to ensure the refinement and standardization of the management process.

Objective:To explore the clinical effects of free bilateral turbocharged anterolateral thigh flaps in tandem in repairing extensive wounds in the foot and ankle.Methods:The study was a retrospective observational study. From April 2020 to June 2023, 12 patients with extensive wounds in the foot and ankle who met the inclusion criteria were admitted to the Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 8 males and 4 females, aged 21 to 65 years. The wound area after debridement ranged from 27 cm×14 cm to 37 cm×20 cm. The bilateral perforator flaps pedicled with either oblique or descending branches of the lateral circumflex femoral artery were designed and harvested based on the size and shape of the wounds. The individual flap incision area ranged from 16 cm×9 cm to 34 cm×12 cm. The non-homologous perforator of the flap on the one side was turbocharged by anastomosing it with the gross muscular branch or main vessel of the oblique or descending branch of the lateral circumflex femoral artery from the flap. Subsequently, the proximal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were connected end-to-end with either the anterior tibial artery and vein, posterior tibial artery and vein, or dorsal foot artery and vein in the recipient area, the distal end of the oblique or descending branch of the lateral circumflex femoral artery and its accompanying vein from the flap on the one side were anastomosed end-to-end with a source vessel originating from flap on the other side. The wounds in the flap donor areas were sutured directly. The number and source of perforators carried by the flaps and the duration of the flap repair surgery were recorded. The survival of the flap, the occurrence of vascular crisis, and the wound healing at both donor and recipient areas were observed after surgery. The flap condition, appearance and function of the affected limb were observed during follow-up. At the last follow-up, the sensory function of the flap was assessed using the British Medical Research Council's sensory rating standard, the foot and ankle function of the affected limb was evaluated according to the American Orthopedic Foot and Ankle Society scoring standard.Results:A total 24 flaps were successfully harvested, carrying 60 perforators, including 34 perforators from the oblique branch of the lateral circumflex femoral artery, 24 perforators from the descending branch of the lateral circumflex femoral artery, one perforator from the transverse branch of the lateral circumflex femoral artery, and one perforator from the direct branch of the femoral artery. The duration of the flap repair surgery ranged from 4.2 to 9.0 hours. The flaps of 12 patients exhibited complete survival after surgery. A total of two flaps of two patients experienced venous crisis after surgery but survived through emergency exploration. One patient encountered undesirable wound healing at the donor area of flap on the one side after surgery, which healed after dressing change, debridement, and suturing. The remaining patients' donor area wounds healed. Two patients displayed impaired wound healing in the recipient area, which improved after dressing change and resection of residual sequestrum, and the wounds in the recipient area of other patients healed successfully. During the follow-up of 4-26 months, the flaps demonstrated favorable color and texture, slight edematous appearance, and partial sensory recovery, as well as good aesthetic and functional restoration of the affected limbs. At the last follow-up, the sensory function of the flap was assessed as grade S2 in 9 cases and grade S3 in 3 cases; the foot and ankle function of the affected limb was evaluated as excellent in two cases, good in 9 cases, and fair in one case.Conclusions:The bilateral turbocharged anterolateral thigh flaps have numerous sources of perforators. By implementing supercharging of non-homologous perforators within the flap, the vascular supply to the flap is turbocharged, thereby mitigating the risk of extensive flap necrosis. The flap is an effective approach for repairing extensive wounds in the foot and ankle, resulting in improved function of the affected limb after repair.