Correlation and risk factors of peripheral and cervicocephalic arterial atherosclerosis in patients with ischemic cerebrovascular disease.

Patients with ischemic cerebrovascular disease (ICVD) frequently develop concomitant peripheral artery disease (PAD) or renal artery stenosis (RAS), and multiterritorial atherosclerotic patients usually have a worse prognosis. We aimed to evaluate the status of peripheral atherosclerosis (AS) and cervicocephalic AS (CAS) in ICVD patients with AS, their correlation, and related risk factors contributing to coexisting cervicocephalic-peripheral AS (CPAS). Based on the severity and extent of AS evaluated by computed tomography angiography and ultrasound, the degree of AS was triple categorized to assess the correlation between CAS and PAD/RAS. CAS and PAD/RAS were defined as the most severe stenosis being ≥ 50% luminal diameter in cervicocephalic or lower limb arteries, and a peak systolic velocity at the turbulent site being ≥ 180 cm/s in the renal artery. Among 403 patients with symptom onset within 30 days, CAS, PAD, and RAS occurrence rates were 68.7%, 25.3%, and 9.9%, respectively. PAD was independently associated with the degree of extracranial and intracranial CAS (p = 0.042, OR = 1.428, 95% CI 1.014-2.012; p = 0.002, OR = 1.680, 95% CI 1.206-2.339), while RAS was independently associated with the degree of extracranial CAS (p = 0.001, OR = 2.880, 95% CI 1.556-5.329). Independent CPAS risk factors included an ischemic stroke history (p = 0.033), increased age (p < 0.01), as well as elevated fibrinogen (p = 0.021) and D-dimer levels (p = 0.019). In conclusion, the occurrence rates of RAS and PAD in ICVD patients with AS is relatively high, and with the severity of RAS or PAD increase, the severity of CAS also increase. Strengthening the evaluation of peripheral AS and controlling elevated fibrinogen might be crucial for preventing and delaying the progression of multiterritorial AS in ICVD patients with AS, thereby improving risk stratification and promoting more effective prevention and treatment strategies.

Effects of calcitonin on lumbar spinal stenosis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. MATERIAL AND METHOD: We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. RESULTS: We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. CONCLUSION: There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.

Evaluating Total Atherosclerosis Burden of Baroreceptor-Resident Arteries after Ischemic Cerebrovascular Disease for Identifying Patients with Heavy Coronary Atherosclerosis Burden.

AIM: The carotid sinuses and aortic arch are baroreceptor-resident arteries (BRAs) and atherosclerosis-susceptible sites of brain-supplying arteries, which would impair baroreflex-mediated blood pressure (BP) regulation and prompt coronary atherosclerosis. We sought to determine the relationship between total atherosclerosis burden (TAB) of BRAs and coronary atherosclerosis burden (AB) in patients with ischemic cerebrovascular disease (ICVD) and explore the potential contribution of BP profiles to this relationship. METHODS: In this cross-sectional analysis of patients with ICVD who simultaneously undertook computed tomography angiography and 24-hour ambulatory BP monitoring, TAB of BRAs was scored based on the atherosclerotic vessel circumference ratio of the carotid sinuses and aortic arch, while the ABs of the intracranial, cervical, aortic, and coronary arteries were scored based on stenosis severity and plaque complexity as routine. RESULTS: Among the 230 patients analyzed, coronary AB was significantly correlated with TAB of BRAs, independently of, and more tightly than the ABs of the intracranial, cervical, and aortic arteries, and the stenosis- and complexity-based AB of BRA-located arteries (bilateral common and extracranial internal carotid arteries and aortic arch). Both coronary AB and TAB of BRAs were negatively associated with the night-to-day BP dipping ratios, which was quite different from the relationship between intracranial AB and 24-hour BP characteristics. These findings were also true for patients with ICVD without a history of coronary artery disease. CONCLUSION: Evaluating TAB of BRAs might provide a new link between atherosclerosis of brain- and heart-supplying arteries, connected partially by BP circadian rhythm. It might facilitate identifying patients with ICVD with heavy coronary AB and comprehensively managing vascular risk.

Profibrotic role of transcription factor SP1 in cross-talk between fibroblasts and M2 macrophages.

Fibrosis disrupts tissue balance and links to severe illnesses, impairing organ function and, in some cases, even fatality. The interaction between M2 macrophages and fibroblasts is vital for tissue equilibrium. Transforming growth factor ß1 (TGF-ß1) released by M2 macrophages plays a central role in fibrosis, regulating fibroblast activity and extracellular matrix metabolism. Targeting TGF-ß1 is key to fibrosis treatment. In our study using three fibroblast cell lines, we reveal that the M2 macrophage transcription factor SP1 enhances binding to the TGF-ß1 promoter motif, promoting TGF-ß1 transcription and activating fibroblasts (This process does not involve changes in DNA methylation levels surrounding the motif sequence). The zinc fingers in SP1's DNA-binding domain 3 are crucial for this binding. In vivo, targeting SP1 in rat ligaments significantly reduces extracellular matrix accumulation. Our findings highlight SP1 as a promising target for regulating tissue extracellular matrix and combating fibrosis.

[Analysis of clinical efficacy and risk factors of relapse in young patients with cervical instability treated by manipulation].

OBJECTIVE: To determine the clinical efficacy of different manipulation in the treatment of cervical instability in young people, and to analyze the risk factors of relapse of cervical instability in young people. METHODS: From March 2021 to June 2022, the clinical data of 120 young patients with cervical instability were retrospectively analyzed. According to the different treatment methods, they were divided into rotation group (60 cases, 3 cases of loss) and tendon group (60 cases, 5 cases of loss). There were 25 males and 32 females in rotation-traction manipulation group;age ranged from 22 to 44 years old with a median of 28 years old;course of disease ranged from 0.17 to 120 months with amedian of 22 months. There were 22 males and 33 females in tendon-regulating manipulation group;age ranged from 21 to 42 years old with a median of 27 years old;course of disease ranged from 0.23 to 180 months with a median of 24 months. Both groups were treated for 2 weeks, once every other day for 7 times, and were followed up for 1 year. The clinical efficacy of the two groups was evaluated, and the visual analogue scale (VAS), neck disability index (NDI) were observed before and after treatment. One year after the course of treatment, patients with effective treatment were followed up to make statistics on recurrence. Patients with recurrence were included in the recurrence group, while those without recurrence were included in the non-recurrence group. Factors that may affect symptom recurrence were analyzed, and univariate and multivariate Logistic regression analysis were performed. RESULTS: The 13 patients who failed the treatment (4 cases in the rotation-traction manipulation group and 9 cases in the tendon-regulating manipulation group) were not followed up. All the 99 patients who were effective in treatment were followed up ranged from 303 to 406 days with a median of 359 days. No complications occurred in all patients. There were significant differences in VAS and NDI between the two groups after treatment and before treatment (P<0.05), and there were significant differences in VAS and NDI between the two groups after treatment (P<0.05). Ninety-nine patients achieved follow-up, 56 (56.57%) relapsed and 43 (43.43%) did not. Univariate correlation analysis showed that NDI index, the time spent at the desk every day, the time spent using electronic products every day and angular displacement of anterior flexion before treatment in the relapse group were significantly higher than those in the non-relapse group (P<0.05). Logistic regression analysis showed that the time spent at the desk every day [OR=2.447, 95%CI(1.255, 4.771)], the time spent using electronic products every day [OR=1.892, 95%CI(1.066, 3.358)] and the angular displacement of anterior flexion of the cervical before treatment [OR=1.246, 95%CI(1.045, 1.485) ]were the risk factors for relapse. CONCLUSION: Both rotation-traction manipulation and tendon-regulating manipulation can effectively treat cervical instability in young people, and rotation-traction manipulation has more advantages than tendon-regulating manipulation in improving cervical pain and cervical dysfunction in patients. The time spent at the desk every day, the time spent using electronic products every day, and the increase of cervical flexion angle displacement will increase the risk of relapse in patients.

[Comparison of clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle and distal tibia fractures].

OBJECTIVE: To compare the clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle anddistal tibia fractures. METHODS: The clinical data of sixty patients with middle and distal tibia fractures admitted between January 2019 and November 2022, were retrospectively analyzed. These patients were categorized into external fixation group (n=30) and internal fixation group (n=30). There were 18 males and 12 females in the external fixation group, with an average age of (49.29±2.35) years old. Among them, 14 patients presented with fractures on the left side, and 16 patients presented with fractures on the right side. Closed reduction, arched wire, and semi-circular external fixator were used for treatment. There were 20 males and 10 females in the internal fixation group, with an average age of (48.96±1.87) years old. Among them, 15 patients presented with fractures on the left side, and 15 patients presented with fractures on the right side. MIPPO technique was used for the treatment. Perioperative parameters, including time injury to surgery, surgical duration, incision length, intraoperative bleeding, time to active activity, and incision healing level, were compared between the two groups. Clinical outcomes were also assessed, including Johner-Wruhs scores, time to minimum pain-adapted full weight-bearing, visual analog scale (VAS), SF-36 scale, and complications. RESULTS: The external fixation group exhibited a significantly shorter incision length (1.36±0.86) cm and lower intraoperative bleeding (10.83±5.73) ml compared to the internal fixation group (12.74±3.12) cm and (86.47±8.90) ml, respectively(P<0.05). The postoperative active activity time (1.50±0.54) days and minimum pain-adapted full weight-bearing activity time(108.87±3.43) days in the external fixation group were slightly delayed than the internal fixation group(1.15±0.98) days and (105.27±3.68) days, respectively(P<0.05). Over a mean postoperative follow-up duration of (6.23±1.89) months, both groups showed improved VAS and SF-36 scale scores. There were no statistically significant differences in VAS and SF-36 scale scores 1, 3, 6 months post-operatively between the two groups(P>0.05). The intraoperative surgical time in the external fixation group (35.42±9.31) minutes was shorter than that in the internal fixation group(74.22±7.81) minutes (P<0.05). There was no intraoperative vascular or nerve injury, nor postoperative skin necrosis in the external fixation group. However, skin necrosis was observed in 6 patientsin the internal fixation group, representing a statistically significant difference (P<0.05). CONCLUSION: Both external fixation and plate internal fixation are effective methods for the treatment of middle and distal tibia fractures. External fixation exhibits the advantage of less surgical trauma and a lower incidence of complications.

Atherosclerosis Burden of Brain- and Heart-Supplying Arteries and the Relationship With Vascular Risk in Patients With Ischemic Stroke.

Background Atherosclerosis of brain- and heart-supplying arteries (BHAs) are risk indicators for patients with ischemic stroke, but the atherosclerosis burden (AB) of intracranial, cervical, aortic, and coronary arteries in each and in total have not been simultaneously evaluated, and the associations with vascular risk remain unknown. Methods and Results With computed tomography angiography, single-territory AB was triple ranked on the basis of the number of arterial segments with a significant atherosclerotic lesion. The total AB (TAB) of BHAs was triple ranked on the basis of the number of arterial territories with a significant atherosclerotic lesion, or according to the sum of 4 single-territory AB rank-scores. After a 12-month follow-up of 395 patients with ischemic stroke, a composite outcome of ischemic stroke, myocardial infarction, and vascular death occurred in 10.9%. The single-territory AB of intracranial, cervical, aortic, and coronary arteries showed distinct strata patterns and different associations with vascular risk. The score-based TAB of BHAs predicted vascular risk (crude hazard ratios [95% CIs]: per level increase, 2.35 [1.54-3.58]; median versus low, 3.37 [1.45-7.82]; high versus low, 6.00 [2.36-15.24]) independently of vascular risk factors and single-territory AB, providing more prognostic information than the TAB of BHAs measured by the number of significantly atherosclerotic territories. Vascular events occurred in 3.0%, 13.6%, and 22.6% of patients in the low (41.8%), median (44.8%), and high (13.4%) strata of the score-based TAB of BHAs, respectively. Conclusions The single-territory AB of intracranial, cervical, aortic, or coronary arteries might be not reliable for vascular risk stratification in patients with ischemic stroke, and evaluating the TAB of BHAs by quantitatively integrating the single-territory AB is advisable.

Early identification and treatment for peripheral arterial disease in patients with ischemic cerebrovascular disease.

Ischemic cerebrovascular disease (ICVD) is a major cause of mortality and disability worldwide and is often caused by atherosclerosis. As a systemic disease, atherosclerosis usually affects multiple vascular beds, mainly including cerebral, coronary, and peripheral arteries. Therefore, ICVD is easily complicated by lower-extremity peripheral arterial disease (PAD). ICVD patients with PAD have more serious symptoms and a worse prognosis, however, neurologists might neglect the evaluation and management of the coexistent PAD, and there is still a lack of consensuses about the diagnosis and treatment for such patients. By summarizing relevant research progresses, this review showed that duplex ultrasound had more advantages in the early screening and evaluation of PAD in ICVD patients among multiple methods to diagnose PAD. Furthermore, the current evidence seems to support that single-drug antiplatelet can be used as the basic treatment, and new antithrombotic strategies, such as ticagrelor only or aspirin combined with low-dose rivaroxaban are expected to further reduce the incidence of stroke for ICVD patients with PAD. More effective treatments would be explored by large-scale trials to guide the clinical management to prevent secondary stroke for such patients.

Bias and Reporting Quality of Clinical Prognostic Models for Idiopathic Pulmonary Fibrosis: A Cross-Sectional Study.

Objective: This study aims to evaluate the risk of bias (ROB) and reporting quality of idiopathic pulmonary fibrosis (IPF) prediction models by assessing characteristics of these models. Methods: The development and/or validation of IPF prognostic models were identified via an electronic search of PubMed, Embase, and Web of Science (from inception to 12 August, 2021). Two researchers independently assessed the risk of bias (ROB) and reporting quality of IPF prediction models based on the Prediction model Risk Of Bias Assessment Tool (PROBAST) and Transparent Reporting of a multivariable prognostic model for Individual Prognosis or Diagnosis (TRIPOD) checklist. Results: Twenty prognostic model studies for IPF were included, including 7 (35%) model development and external validation studies, 8 (40%) development studies, and 5 (25%) external validation studies. According to PROBAST, all studies were appraised with high ROB, because of deficient reporting in the domains of participants (45.0%) and analysis (67.3%), and at least 55% studies were susceptible to 4 of 20 sources of bias. For the reporting quality, none of them completely adhered to the TRIPOD checklist, with the lowest mean reporting score for the methods and results domains (46.6% and 44.7%). For specific items, eight sub-items had a reporting rate ≥80% and adhered to the TRIPOD checklist, and nine sub-items had a very poor reporting rate, less than 30%. Conclusion: Studies adhering to PROBAST and TRIPOD checklists are recommended in the future. The reproducibility and transparency can be improved when studies completely adhere to PROBAST and TRIPOD checklists.

[Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis].

OBJECTIVE: To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS). METHODS: From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded. RESULTS: There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group. CONCLUSION: Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Circular RNA circLDB2 functions as a competing endogenous RNA to suppress development and promote cisplatin sensitivity in non-squamous non-small cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs) are covalently closed RNAs and are implicated in the development of non-small cell lung cancer (NSCLC). Here, we identified the precise actions of circRNA LIM domain binding 2 (circLDB2, hsa_circ_0069244) in non-squamous NSCLC development and drug sensitivity. METHODS: CircLDB2, microRNA (miR)-346, and LIM and calponin-homology domains 1 (LIMCH1) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease R (RNase R), actinomycin D, and subcellular localization assays were used to characterize circLDB2. Cell proliferation and viability, colony formation, apoptosis, migration, and invasion were gauged by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing, and transwell assays, respectively. RNA immunoprecipitation (RIP), RNA pull-down, and dual-luciferase reporter assays were used to verify the direct relationship between miR-346 and circLDB2 or LIMCH1. Animal studies were performed to evaluate the impact of circLDB2 in vivo. RESULTS: CircLDB2 was underexpressed in non-squamous NSCLC and was identified as a bona fide circular transcript. Overexpression of circLDB2 impeded cell proliferation, migration, invasion, and enhanced apoptosis and cisplatin sensitivity in vitro, as well as promoted the antitumor effect of cisplatin in vivo. CircLDB2 regulated cell functional behaviors and cisplatin sensitivity by sponging miR-346. LIMCH1 was a direct and functional target of miR-346. Furthermore, circLDB2 acted as a competing endogenous RNA (ceRNA) for miR-346 to induce LIMCH1 expression. CONCLUSION: Our findings demonstrated that circLDB2 impeded non-squamous NSCLC development and enhanced cisplatin sensitivity partially by acting as a ceRNA, highlighting circLDB2 as a promising candidate for the development of novel antitumor therapies.