BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Diabetic peripheral neuropathy (DPN) is one of the common chronic complications of diabetes, presenting with neuropathic pain, sensory abnormalities, and sensory loss, and may lead to foot infections, ulcers, or amputation in severe cases. Its pathogenesis remains unclear, with challenge in early diagnosis and limited treatment efficacy. Emerging evidences suggest that DPN involves in not only the peripheral nervous system but also the central nervous system (CNS). With advances in imaging technologies, multimodal MRI has become a key tool to investigate CNS involvement in DPN. This review summarizes the structural, functional, metabolic, and perfusion-related CNS changes in DPN patients based on structural MRI, functional MRI, MR spectroscopy, and perfusion-weighted imaging, aiming to help early detection, clinical subtyping, and personalized treatment of DPN.

Peripheral neuropathic pain (PNP) patients exhibit complex and diverse symptoms, often accompanied by abnormal pain and hyperalgesia, which seriously affect their quality of life. Currently, pharmacological treatments for PNP have limited effectiveness and are prone to side effects, making them inadequate for long-term patient needs. Peripheral nerve stimulation (PNS) can relieve pain by precisely stimulating specific peripheral nerves, offering advantages such as minimal invasiveness, broad applicability, and personalized treatment. This article reviews the pathophysiology of PNP and application of PNS in PNP treatment, aiming to provide references for PNP treatment.

Objective:To explore the impact of air pollution on hospital visits for mental and behavioral disorders among residents in an industrial area in Henan Province from 2016 to 2021.Methods:Daily outpatient visits data for mental and behavioral disorders were collected from Angang General Hospital in Angang Industrial Area at Anyang City between January 2016 and December 2021. And air pollutants and meteorological data during the same period were also collected. A generalized additive model was used for time-series analysis to examine the relationship between daily average concentrations of nitrogen dioxide (NO 2), sulfur dioxide (SO 2), fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), carbon monoxide (CO), and ozone (O 3) with a lag of 0 to 7 days on the number of visits for mental and behavioral disorders among residents. The single-day lag effect (lag0-lag7 d) and cumulative lag effect (lag01-lag07 d) were analyzed. The smooth cubic spline function was used to fit the exposure-response relationship, and subgroup analysis was performed according to different genders, seasons and ages. Results:A total of 26 268 hospital visits for mental and behavioral disorders were collected from the industrial area between 2016 and 2021. The daily average concentrations of SO 2, NO 2, PM 2.5, PM 10, and CO were (27.50±27.33), (43.11±18.33), (73.87±60.30), (134.01±83.81) μg/m 3, and (1.72±1.03) mg/m 3, respectively. The daily maximum 8-hour average concentration of O 3 was (82.18±53.70) μg/m 3. After controlling for long-term trends, temperature, relative humidity, day of the week effects, and holiday effects, the generalized additive model analysis showed that NO 2 had a statistically significant impact on the hospital visits for mental and behavioral disorders at lag0 d, lag2 d and lag01-lag05 d and CO had a statistically significant impact at lag0-lag3 d and lag01-lag06 d (all P<0.05). NO 2 at lag02-lag04 d and CO at lag0-lag2 d and lag01-lag04 d had statistically significant effects on the visits for neurasthenia (both P<0.05). The impacts of NO 2 at lag03-lag04 d, PM 2.5 at lag3 d and lag03-lag04 d, PM 10 at lag3 d and lag03 d, and CO at lag3 d and lag01-lag05 d on visits for generalized anxiety disorder were also statistically significant (all P<0.05). After false discovery rate (FDR) correction, it was shown that for every 10 μg/m 3 increase in NO 2 and every 0.1 mg/m 3 increase in CO, the percentage increase in visits for mental and behavioral disorders and its 95% confidence interval (95% CI) were 3.38% (0.95%-5.87%) and 0.78% (0.38%-1.17%), respectively. For every 0.1 mg/m 3 increase in CO, the visits for neurasthenia increased by 0.78% (0.27%-1.29%). For every 10 μg/m 3 increase in PM 2.5 and every 0.1 mg/m 3 increase in CO, the visits for generalized anxiety disorder increased by 1.07% (0.46%-1.68%) and 1.17% (0.37%-1.97%), respectively (adjusted P<0.05). There was a linear exposure-response relationship between NO 2 and CO and the hospital visits for mental and behavioral disorders, CO and the hospital visits for neurasthenia, and CO and PM 2.5 and the hospital visits for generalized anxiety disorder ( P<0.05 for the overall association test and P>0.05 for the non-linearity test). Stratified analysis showed that air pollutants had an impact on male patients with neurasthenia, female patients with generalized anxiety disorder, individuals aged <45 years with mental and behavioral disorders, and individuals aged ≥65 years with generalized anxiety disorder. The impact of air pollutants was greater during the cold season or winter. Conclusion:Exposure to air pollution can increase hospital visits for mental and behavioral disorders among residents in industrial areas, with a higher risk among those aged<45 years old and during the cold season.

Objective To analyze the effects of fluid overload(FO)on clinical outcomes of extremely preterm infants with hemody-namically significant patent ductus arteriosus(hsPDA).Methods This retrospective study analyzed data from neonates ≤ 32 weeks ges-tational age(GA)admitted to the Neonatal Intensive Care Unit(NICU)of the Affiliated Hospital of Xuzhou Medical University between November 2021 and July 2024.Infants were categorized into hsPDA and non-hsPDA groups based on the presence or absence of hsPDA.General clinical data and daily FO situation in the first week after birth of the two groups were compared,and the risk factors affecting hsPDA were obtained by Logistic regression analysis.Using the first day of postnatal FO as the test variable and hsPDA as the state varia-ble,receiver operator characteristic(ROC)curve was drawn to calculate the cut-off value of FO,and the cut-off value was divided into groups to analyze the relationship between the first day FO and clinical outcome of very preterm infants.Results A total of 153 extremely preterm infants(GA≤32 weeks)were enrolled,including 110 in the hsPDA group and 43 in the non-HSPDA group.Univariate analysis showed that there were statistically significant differences in birth weight,1-minute Apgar score,postnatal antibiotic use time,parenteral nutrition time,invasive mechanical ventilation time,non-invasive mechanical ventilation time,hospital days,day 1,day 2 and day 4 FO between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that invasive mechanical ventilation time and day 1 FO were risk factors of hsPDA.The ROC curve was drawn with the first day FO as the test variable and hsPDA as the state variable.The area under the curve was 0.903,the sensitivity and specificity were 79.1％and 89.1％,respectively,and the cut-off value of FO on the first day after birth was 8.78％.According to this cut-off value,107 cases were divided into FO≤8.78％group and 46 cases were FO＞8.78％group.Univariate analysis showed that FO＞8.78％group had lower Apgar score at 1 minute,longer invasive mechani-cal ventilation time,and higher incidence of moderate to severe bronchopulmonary dysplasia(BPD)and grade 3 to 4 intraventricular hem-orrhage(IVH).Logistic regression analysis showed that FO＞8.78％on the first day after birth was a risk factor for moderate to severe BPD and grade 3-4 IVH.Conclusion FO＞8.78％on the first day after birth of very preterm infants increased the incidence of moder-ate to severe BPD and grade 3-4 IVH.

Objective To quantitatively evaluate the structure and content of the long-term care insurance(LTCI)policy in China's deeply aging areas.Methods Using the Policy Modeling Consistency(PMC)index model indicator design method,a LTCI policy evalua-tion index system was constructed,consisting of nine primary indicators and 34 secondary indicators.A total of 123 provincial-level LTCI policies issued in deeply aging regions of China between June 1,2014,and October 1,2024 were analyzed.High-frequency word extraction was performed using ROSTCM 6.0,and a social network diagram of LTCI policies was created.The policy structure and content were quantitatively evaluated and ana-lyzed based on the established policy evaluation index system.Results The main content of LTCI policies in deeply aging areas of China covered services,institutions and assessment.The highest policy score was 7.28,and the lowest was 2.20,with an average score of 5.00.There were 25 perfect policies,63 excellent policies,28 good policies and seven qualified policies.In the dimension of policy content,the indexes of five primary indicators of policy evaluation,policy target groups,policy nature,policy perspective and policy tools were 0.60 or more;while the indexes of four primary indicators of policy content,incentives and constraints,policy timeliness,and policy level were 0.50 or less.Conclusion LTCI policies issued in China's deeply aging areas provide comprehensive coverage in aspects such as poli-cy evaluation,policy target groups and policy nature,and need to be improved in policy tool selection and the construction of incentive and constraint mechanisms.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Tooth extraction is one of the most common procedures in oral surgery.Poor wound healing is a common problem after tooth extraction.Poor wound healing may not only lead to eating difficulties and impaire psychological health,but also increase the difficulty and cost of treatment,prolong the treatment period and lead to osteonecrosis of the jaw in severe cases.Currently,there is a lack of systematic integration and evaluation of domestic and international studies related to post-extraction wound healing.In this study VOSviewer,Bibliometrix and CiteSpace software were used to econometrically analyse the literature on post-extraction wound healing from 2013 to 2023,with the aim of providing a reference for developing more scientific and systematic strategies for post-ex-traction wound management and prevention of the complications.

Objective To analyze the effects of fluid overload(FO)on clinical outcomes of extremely preterm infants with hemody-namically significant patent ductus arteriosus(hsPDA).Methods This retrospective study analyzed data from neonates ≤ 32 weeks ges-tational age(GA)admitted to the Neonatal Intensive Care Unit(NICU)of the Affiliated Hospital of Xuzhou Medical University between November 2021 and July 2024.Infants were categorized into hsPDA and non-hsPDA groups based on the presence or absence of hsPDA.General clinical data and daily FO situation in the first week after birth of the two groups were compared,and the risk factors affecting hsPDA were obtained by Logistic regression analysis.Using the first day of postnatal FO as the test variable and hsPDA as the state varia-ble,receiver operator characteristic(ROC)curve was drawn to calculate the cut-off value of FO,and the cut-off value was divided into groups to analyze the relationship between the first day FO and clinical outcome of very preterm infants.Results A total of 153 extremely preterm infants(GA≤32 weeks)were enrolled,including 110 in the hsPDA group and 43 in the non-HSPDA group.Univariate analysis showed that there were statistically significant differences in birth weight,1-minute Apgar score,postnatal antibiotic use time,parenteral nutrition time,invasive mechanical ventilation time,non-invasive mechanical ventilation time,hospital days,day 1,day 2 and day 4 FO between the two groups(P＜0.05).Multivariate Logistic regression analysis showed that invasive mechanical ventilation time and day 1 FO were risk factors of hsPDA.The ROC curve was drawn with the first day FO as the test variable and hsPDA as the state variable.The area under the curve was 0.903,the sensitivity and specificity were 79.1％and 89.1％,respectively,and the cut-off value of FO on the first day after birth was 8.78％.According to this cut-off value,107 cases were divided into FO≤8.78％group and 46 cases were FO＞8.78％group.Univariate analysis showed that FO＞8.78％group had lower Apgar score at 1 minute,longer invasive mechani-cal ventilation time,and higher incidence of moderate to severe bronchopulmonary dysplasia(BPD)and grade 3 to 4 intraventricular hem-orrhage(IVH).Logistic regression analysis showed that FO＞8.78％on the first day after birth was a risk factor for moderate to severe BPD and grade 3-4 IVH.Conclusion FO＞8.78％on the first day after birth of very preterm infants increased the incidence of moder-ate to severe BPD and grade 3-4 IVH.