This article explores the pathogenesis ， evolution and the prevention-treatment strategies of hypertension-related coronary microvascular dysfunction （H-CMD） from the collateral disease theory. Long-term hypertension may lead to coronary microvascular vasomotor imbalance， endothelial injury， vascular remodeling， microthrombosis， reduced perfusion reserve， and microvascular rarefaction， suggesting a progressive pathological process from functional disturbance to structural injury， collateral obstruction， and insufficient repair. Collateral disease theory emphasizes the network-like distribution， gradual branching， and permeating and nourishing functions of collaterals， as well as the concept that prolonged disease enters the collaterals， providing a reference for understanding coronary microcirculatory dysfunction and malnourishment of heart collaterals. Accordingly， the traditional Chinese medicine （TCM） pathogenesis of H-CMD can be summarized into four interconnected stages： Collateral Qi stagnation， scorching injury of collateral vessels， phlegm-stasis obstruction of collaterals， and collateral deficiency with malnourishment. Collateral Qi stagnation is the initiating stage， mainly corresponding to abnormal coronary microvascular vasomotor regulation and endothelial dysfunction. Scorching injury of collateral vessels represents the developmental stage and is closely associated with inflammation， oxidative stress， and endothelial barrier injury after Qi stagnation transforms into fire. Phlegm-stasis obstruction of collaterals represents the prolonged stage and may aggravate vascular wall thickening， luminal stenosis， microthrombosis， and insufficient microcirculatory perfusion. Collateral deficiency with malnourishment is the late-stage outcome， reflecting deficiency of healthy Qi， collateral damage， Qi-blood malnourishment， and weakened repair capacity， mainly manifested as microvascular rarefaction， occlusion， and microcirculatory homeostatic imbalance. Therapeutically， stage-based syndrome differentiation and the combined strategy of dredging and nourishing collaterals should be emphasized. Specifically， promoting Qi movement， resolving stagnation， soothing the liver， and harmonizing collaterals should be adopted in the early stage. Clearing heat， pacifying the liver， calming and protecting collaterals should be adopted in the developmental stage. Resolving phlegm， activating blood， and dredging collaterals should be implemented in the prolonged stage. Supplementing Qi， nourishing blood， tonifying the kidney， regulating balance， strengthening healthy Qi， and nourishing collaterals should be carried out in the late stage. Related formulas and medicinals may act by regulating the nitric oxide/endothelin-1（NO/ET-1） balance， inhibiting inflammation and oxidative stress， improving microcirculatory perfusion， and promoting angiogenesis and endothelial repair. Collateral disease theory may provide a theoretical basis for understanding the dynamic pathogenesis of H-CMD and for stage-based TCM intervention.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Chronic low back pain (CLBP) is a pervasive and debilitating condition, affecting millions of individuals globally and imposing a significant burden on healthcare systems. Traditional treatment modalities often have limited efficacy, leading to the exploration of novel therapeutic interventions. Endoscopic rhizotomy (ER) has emerged as a promising technique, particularly for managing facetogenic pain. This systematic review presents a comprehensive overview of the historical evolution, current practices, and clinical outcomes associated with ER in the treatment of CLBP. This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials, covering publications up to February 1, 2024, utilizing specific keywords related to low back pain (LBP) and full-endoscopic lumbar rhizotomy. Data extraction focused on patient demographics, clinical outcomes, and any reported complications associated with this procedure. Ten selected studies, comprising a total of 529 patients, were included. Approximately 96.7% to 97.8% of patients who underwent ER reported excellent or good results based on the MacNab score. Patients treated with ER demonstrated significantly better visual analogue scale scores (mean difference: -2.39; 95% confidence interval [C]I, -3.15 to -1.63; p<0.00001) and showed greater improvement on the Oswestry Disability Index (mean difference: -19.97; 95% CI, -37.48 to -2.46; p=0.03) than those treated with traditional percutaneous radiofrequency ablation (TPRA). No major postoperative complications were reported. Full-endoscopic lumbar rhizotomy represents a significant advancement in the treatment of CLBP, especially in cases involving facetogenic pain. The procedure offers superior outcomes compared to TPRA, with higher patient satisfaction rates and improved clinical outcomes. The absence of major complications highlights its potential as a therapeutic option for facetogenic LBP. However, the findings are limited by the small number of studies, varying follow-up durations, and potential publication bias.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

The presence of 4-aminophenol(4-AP)in wastewater from the pharmaceutical industry is a common occurrence due to its role as a byproduct or intermediate during the hydrolysis process of paracetamol metabolism,resulting in significant water pollution.Therefore,it is crucial to employ a straightforward and reliable analytical approach for detecting 4-AP in the environment.In this study,a specific type of metal-organic framework(MOF)material called[Cd4(ABTC)2(H2O)12]n(SXNU-4-Cd,H4ABTC=3,3′,5,5′-azobenzene tetracarboxylic acid)was successfully synthesized,which exhibited a unique two-dimensional layered structure consisting of three intertwined spiral chains forming a distinctive″twist braid″.These layers underwent π-π stacking,creating three-dimensional channels with azo bonds decorating the channel walls.This p-π interaction significantly enhanced the adsorption capacity of SXNU-4-Cd towards 4-AP,thereby improving its recognition sensitivity.The fabricated SXNU-4-Cd/GCE sensor showed high sensitivity towards 4-AP in the linear concentration range of 0.1-130 μmol/L,with a detection limit of 8.6 nmol/L,and also exhibited good anti-interference capability,reproducibility and stability.The SXNU-4-Cd/GCE sensor was successfully used for detecting 4-AP in lake water sample,with spiked recoveries of 95.9%-102.8%.This study introduced a novel technique that utilized pure Cd-MOFs to develop electrochemical sensor capable of effectively detecting 4-AP in water samples.

In the process of murder investigation,it is of great significance to find the discarded and buried human remains accurately.The main methods of searching for human remains include human vi-sual search,aerial detection,geophysical technology,remote imaging technology and canine olfactory search technique.Canine olfactory search for human remains is a recognized time-effective and non-invasive search method,making dogs the most valuable search tool in forensic investigation.By sys-tematically reviewing and summarizing relevant literature,and based on the theory of volatile organic compound produced by the decomposition of human remains,this paper explores the basic principle of the canine olfactory search technique for human remains.This paper also reviews the application of training canine search technique for human remains in forensic investigation by using human blood,tissue,cadaver putrefying fluid and odor substitutes as sniffing sources.The application prospect of canine olfactory search for human remains was prospected from the perspectives of detection of vola-tile organic compound during cadaver decay,development of odor substitutes and adsorption devices,and technology tactics used in canine training and use,to provide references for the relevant research of canine olfactory search for human remains in China.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.