OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Pregnancy complicated by aortic root aneurysm in patients with Marfan syndrome is one of the main causes of termination of pregnancy or even death in pregnant women. A very small number of pregnant women require cardiac surgery to preserve pregnancy under extracorporeal circulation, and all surgeries use aortic root replacement. We reported a 30-year-old patient with severe aortic regurgitation combined with giant aortic root aneurysm and Marfan syndrome in mid-pregnancy. Valve-sparing root replacement using reimplantation technology was performed via a multidisciplinary cooperation model. This not only achieved the patient’s desire to continue pregnancy but also avoided the anticoagulation and bleeding complications brought by mechanical valve replacement, reduced pregnancy risks and improved long-term quality of life. Postoperative echocardiography showed a small amount of aortic valve regurgitation, aortic valve coaptation height of 0.6 cm, effective height of 1.1 cm, maximum aortic flow velocity of 1.4 m/s, mean transvalvular pressure gradient of 4.4 mm Hg, and satisfactory clinical results.

[Objective] To compare the efficacy and safety of deglycerolized red blood cells (DRBC) and suspended red blood cells (SRBC) based on the propensity score matching (PSM) method, so as to provide evidence for the rational use of DRBC resources in clinical practice. [Methods] A total of 89 patients who received DRBC transfusion and 2 916 patients who received SRBC transfusion in our hospital from January 2023 to September 2024 were included. A 1∶1 nearest neighbor PSM was used to balance covariates such as gender, age, and body mass index (BMI). The changes of hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and inflammatory markers such as white blood cell (WBC) count, neutrophil (NE) count, C-reactive protein (CRP), and Interleukin-6(IL-6) in the last 72 hours after transfusion were analyzed by SPSS 26.0 and R software to evaluate clinical efficacy and transfusion safety. [Results] The baseline of the two groups was balanced after PSM (P>0.05). There was no significant difference in the total effective rate between the DRBC group (80.9%) and the SRBC group (86.5%) (P>0.05). In the SRBC group, WBC (×10 /L) increased from 9.634±6.742 to 10.147±6.835, CRP (mg/dL) increased from 5.468±4.647 to 6.174±6.114, and IL-6(pg/mL) decreased from 213.733±587.191 to 157.255±552.626. In the DRBC group, WBC (×10 /L) decreased from 11.123±7.880 to 11.011±8.549, CRP (mg/dL) decreased from 5.729±4.761 to 5.326±4.466, and IL-6(pg/mL) decreased from 238.806±639.060 to 152.255±266.558. Compared with the before treatment, the differences between the SRBC group and DRBC group were not statistically significant (P>0.05). Among all patients included in the statistics, the overall incidence of transfusion adverse reactions was 0.205% (6/2 916) in the SRBC group, and no adverse reactions occurred in the DRBC group. The incidence in the SRBC group was higher than that in the DRBC group. [Conclusion] Based on PSM analysis, there was no significant difference in the efficacy and safety of DRBC transfusion compared with SRBC transfusion, which can provide evidence-based support for routine application.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.