PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals ; Rats, Sprague-Dawley ; Rotator Cuff Injuries/surgery* ; Amnion/transplantation* ; Rats ; Wound Healing ; Rotator Cuff/surgery* ; Male ; X-Ray Microtomography ; Tendons/surgery* ; Biomechanical Phenomena

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of Aconitum carmichaelii was selected as the research object. Its ¹H-¹³C HSQC, ¹H-¹H COSY, HMBC, and NOESY spectra were acquired by US and NUS methods, respectively. By comparing the integral values of NMR signals of three chemical groups in fuziline, it is confirmed that the NUS technique has the advantages of improving the quality of 2D NMR spectra and shortening the acquisition time in structure elucidation of small molecule compounds. In HMBC spectrum, it was further confirmed that NUS technology can improve the quality of the 2D spectra and the signal resolution. This indicates that NUS technology can improve the efficiency and reliability of the structure elucidation of small molecule compounds.

AIM:To evaluate the characteristics of ocular biometric parameters and the distribution of corneal astigmatism(CA)in patients with high myopia before cataract surgery.METHODS:A prospective cross-sectional study was conducted, and 695 cataract patients(695 eyes)with high myopia [defined as an axial length(AL)≥26.00 mm] scheduled to undergo cataract surgery at our hospital from January 2022 to December 2024 were consecutively enrolled, another 695 cataract patients(695 eyes)with normal ALs(22.00 mm ≤AL≤25.00 mm)who underwent cataract surgery at our hospital during the same period were included in the control group. For patients with both eyes eligible, the right eye was used for analysis. Before cataract surgery, IOL Master 700 was used to measure the ocular biometric parameters of both eyes for each patient in the two groups. The medical records and ocular biometric data in the two groups were recorded and collected.RESULTS:There were no statistically significant differences between the two groups in genger, age, corneal diameter, and central corneal thickness(all P>0.05). In the high myopia group, the mean AL was 29.20±2.61 mm, and 252 eyes(34.1%)had AL ≥30.00 mm(extremely high myopia). The mean anterior chamber depth(ACD), lens thickness, vitreous chamber depth(VCD), CA, AL/corneal radius of curvature and VCD/AL in the high myopia group were 3.45±0.40, 4.41±0.47, 21.34±2.60 mm, 1.18±0.78 D, 3.79±0.38, and 0.73±0.03, respectively, which were all greater than those in the control group(all P<0.01). In the high myopia group, 350 eyes(50.4%)had CA ≥1.00 D, 192 eyes(27.6%)had CA ≥1.50 D, and 94 eyes(13.5%)had CA ≥2.00 D, which were all higher than those in the control group(32.8%, 15.1%, and 6.6%, respectively; all P<0.001). In the high myopia group, 87 eyes(12.5%)had flat corneas, 424 eyes(61.0%)had moderate CA, and 40 eyes(5.8%)had high CA. These proportions were all higher than those in the control group(6.0%, 46.9%, and 2.9%, respectively; all P<0.001). In the high myopia group, ACD and ACD/AL were negatively correlated with AL(r=-0.162 and -0.661, respectively; all P<0.001), while both ACD and ACD/AL in the control group were positively correlated with AL(r=0.338 and 0.105, respectively; both P<0.01). In the high myopia group, CA increased with age when the patient's age was ≥50 years(r=0.197, P<0.001), which was consistent with the control group.CONCLUSION: The standardized ocular biometric data of cataract patients with high myopia before cataract surgery are helpful for ophthalmologists to accurately calculate the intraocular lens(IOLs)power and select the appropriate IOL type. The majority of high myopia patients need simultaneous correction of CA during cataract surgery.

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To analyze the effectiveness and safety of low molecular weight heparin(LMWH)combined with urokinase thrombolysis in the treatment of elderly patients with acute ischemic stroke(AIS).Methods A total of 132 elderly AIS patients admitted in Department of Neurology of Wuhan No.1 Hospital from January 2023 to September 2024 were recruited,and randomized into control group,group A,group B and group C,with 33 cases in each group.Besides urokinase thrombolysis as basic treatment,the patients in groups A,B and C were given LMWH within 24,24-47 and 48-72 h after thrombolysis,respectively.After 1 week of treatment,the incidence rate of cerebrovascular re-occlusion was compared among the four groups.Plasma prothrombin time(PT),platelet count(PLT),fibrinogen(Fib),nerve growth factor(NGF),neuron-specific enolase(NSE),neurotrophic factor(NTF)and National Institutes of Health Stroke Scale(NIHSS)score were compared before and after treatment and among the four groups.The incidences of adverse reactions were also compared among them during treatment.Results Compared with the levels before treatment,the levels of NGF and NTF were significantly increased,while the PT,PLT,Fib and NSE levels and NIHSS score were obviously decreased in the four groups after 1 week of treatment(P＜0.05).At 1 week of treatment,group A obtained notably higher NGF and NTF levels,and remarkably lower PT,PLT,Fib and NSE levels and NIHSS score than the other three groups(P＜0.05).So were group B when compared with group C and control groups(P＜0.05),and group C when compared with control group(P＜0.05).There was no statistical significance in the comparison of total incidence rate of adverse reactions during treatment among the four groups(P＞0.05).Conclusion LMWH combined with urokinase thrombolytic therapy can effectively improve the coagulation status and neurological function for elderly AIS patients,and the earlier it is applied,the better the efficacy will be.

Objective:To investigate the effects of remote ischemic preconditioning (RIPC) on myocardial injury after non-cardiac surgery (MINS) in elderly patients with hip fracture.Methods:A prospective randomized controlled trial was conducted on 78 elderly patients with hip fracture admitted to the Seventh Medical Center of the PLA General Hospital between October 2023 and September 2024. The patients were divided into RIPC group and non-RIPC group using a random number table. They were treated with closed reduction internal fixation, open reduction internal fixation, or hip arthroplasty for hip fracture under regional anesthesia. The RIPC group received RIPC intervention on the day before surgery and after entering the operating room on the day of surgery (3 cycles of 5-minute upper limb exsanguination followed by 5-minute reperfusion using an inflatable tourniquet cuff). The non-RIPC group received the same perioperative management as the RIPC group except RIPC. Plasma high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured at admission, immediately after surgery, on the morning of the first postoperative day, and on the morning of the third postoperative day and MINS incidence was calculated based on the hs-cTnI concentrations. The incidence of MINS within 3 days postoperatively and the intraoperative complications were compared in the overall cohort and in age-stratified groups (<80 years, ≥80 years). The local adverse reactions at the RIPC application sites were observed within 3 days after surgery.Results:Among the 78 elderly patients with hip fracture, including 21 males and 57 females, aged 60-99 years [79.5(70.0, 87.0)years], 40 were assigned to the RIPC group and 38 to the non-RIPC group. No significant difference was found in the general data of the two groups. There was no significant difference in the overall MINS incidence between the two groups ( P>0.05). In the patients aged <80 years, no MINS incidence was found (0/21) in the RIPC group, compared with 22% (4/18) in the non-RIPC group ( P<0.05), while in the patients aged ≥80 years, no significant difference in MINS incidence was observed between the two groups ( P>0.05). There were no significant differences in intraoperative complication rates in the overall cohort, patients aged <80 years, or patients aged ≥80 years ( P>0.05). None of the patients had local adverse reactions at the RIPC application sites. Conclusion:For elderly patients with hip fracture who received regional anesthesia, RIPC can significantly reduce the incidence of MINS in patients aged <80 years, but exerts no significant effect on MINS incidence in the overall cohort or in patients aged ≥80 years.