Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

As a vital resource, blood directly impacts the life and health of patients and the continuity of medical care. Given that it can only be obtained through voluntary donations from blood donors, its supply is susceptible to shortages due to various external factors. As the first article in a series introducing the " National Plan for NHS Blood and Transplant and Hospitals to Address Blood Shortage in the United Kingdom", this paper provides a detailed overview of the UK’s emergency management system, with a particular focus on its health emergency management framework. Regarding the UK’s emergency management system, this article elaborates on the regulatory and standards framework and institutional mechanisms for emergency management, non-statutory guidance documents offering preparation and implementation advice, the local resilience forums (LRFs) system enabling cross-departmental and multi-agency emergency coordination and collaboration, the UK government’s capacity-building efforts, as well as emergency response entities and command-and-control mechanisms. Supplementing the preceding review, the article further details the legal basis of the UK’s health emergency system and the core standards framework of national health service (NHS) emergency preparedness, resilience, and response (EPRR), with specific reference to relevant documents.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

As the second installment in our series introducing the UK Blood Shortage Response Plan, this article outlines the UK's blood emergency management framework, including: Business Continuity Management (BCM) for healthcare institutions; Structure of emergency command coordination and participating organizations in the UK; Key components of blood emergency management guidelines. Simultaneously, by detailing the National Blood Transfusion Committee's component agencies, institutional responsibilities, operational requirements and operational remit, it provides deeper insights into the development and functioning of the UK's blood emergency management system, thereby delivering comprehensive foundational knowledge for understanding the implementation of the Blood Shortage Response Plan.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

As the second installment in our series introducing the UK Blood Shortage Response Plan, this article outlines the UK's blood emergency management framework, including: Business Continuity Management (BCM) for healthcare institutions; Structure of emergency command coordination and participating organizations in the UK; Key components of blood emergency management guidelines. Simultaneously, by detailing the National Blood Transfusion Committee's component agencies, institutional responsibilities, operational requirements and operational remit, it provides deeper insights into the development and functioning of the UK's blood emergency management system, thereby delivering comprehensive foundational knowledge for understanding the implementation of the Blood Shortage Response Plan.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.