ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum （ER） stress and reducing urinary protein in the rat model of diabetic nephropathy （DN）. MethodSeventy-five SD rats were randomized into normal， model， low-， medium-， and high-dose （4.37， 8.73， 17.46 g·kg^-1， respectively） modified Shengjiangsan， and irbesartan （0.014 g·kg^-1） groups， with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage， once a day， for 8 consecutive weeks. After the last administration， the levels of glucose （GLU） in the blood， 24-hour urinary protein （24 h-UTP）， and superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in the renal tissue were measured. Hematoxylin-eosin staining， periodic acid-Schiff staining， and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin， podocin， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， and activating transcription factor 4 （ATF4） in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 （Sirt1）， phosphorylated （p）-protein kinase RNA-like endoplasmic reticulum kinase （PERK）， and p-eukaryotic translation initiation factor 2 alpha （eIF2α） in rat kidneys. ResultCompared with the normal group， the modeling caused pathological damage to the kidneys， elevated the levels of GLU and 24 h-UTP （P<0.05）， up-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and down-regulated the protein level of Sirt1 （P<0.05） in rat kidneys. Compared with the model group， modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels （P<0.05）， alleviated the pathological damage in the renal tissue， down-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and up-regulated the protein level of Sirt1 （P<0.05）. ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue， thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.

Background Sleep quality is one of the important factors affecting soldiers’ task performance. Objective To explore the effects of mindful attention awareness, burnout, and occupational stress on sleep quality among soldiers in plateau areas. Methods A total of 1090 soldiers were selected from four units in plateau areas by cluster sampling method and were asked to participate a cross-sectional questionnaire survey using the Pittsburgh Sleep Quality Index (PQSI), Occupational Stress Inventory (OSI), Maslach Burnout Inventory-General Survey (MBI-GS), and Mindful Attention Awareness Scale (MAAS). Correlation analysis, regression analysis, and mediated effect test were conducted for the study. Results Of the 1090 soldiers recruited, 1082 soldiers returned valid questionnaires, and the valid recovery rate was 99.26%. The median (P₂₅, P₇₅) score of PSQI was 4.00 (2.00,7.00), the median score of OSI was 26.00 (17.00, 34.00), the median score of MBI-GS was 3.53 (3.13, 4.00), and the median score of MAAS was 71.00 (59.00, 82.00). The burnout and mindful attention awareness levels varied among military personnel of different age groups (P<0.05), so did the burnout and occupational stress levels among military personnel of different length of service groups (P<0.05), and the occupational stress, PSQI, burnout, and mindful attention awareness levels among military personnel with different educational backgrounds and genders (P<0.05). The results of mediated effect test showed that occupational stress and burnout had both a parallel mediated effect and a sequential mediating effect on the relationship between mindful attention awareness and sleep quality, with effect sizes of 15.3%, 21.5% and 31.8%, respectively. Conclusion There is a mediated effect on the relationship between mindful attention awareness and sleep quality by the occupational stress and burnout of military personnel in plateau areas, and sleep quality is also affected by mindful attention awareness through the chain-mediated effect of occupational stress and burnout.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objectives:To observe and analyze the relationship between thoracolumbar vertebral fractures and vertebral bone structure,as well as stress distribution within ligaments,in order to explore the mechanical mechanisms underlying thoracolumbar vertebral fractures.Methods:Eight healthy young male volunteers were recruited for the study.X-ray and CT examinations of the entire spine were conducted to rule out spinal deformity,tumor,and bone disease.Bone mineral density(BMD)measurements were taken for each vertebral body and femur to exclude osteoporosis.CT thin layer scan was performed from the upper endplate of T11 to lower edge of L2 vertebra,and the CT image parameters were imported to ABAQUS 2016 software to standardize and perform finite element mesh construction.The thoracolumbar spine finite element model was developed using MIMICS 17.0,GEOMAGICS 15.0,and PRO/ENGINEER 5.0 softwares to measure relevant parameters,and its efficacy was validated.Seven motion states,including vertical compression,flexion,extension,left and right lateral bending,and left and right rotation,were simulated.ABAQUS software was employed to analyze stress distribution patterns and variations in the seven motion states of the finite element model,allowing for the observation of the relationship between stress distribution and thoracolumbar fracture.Results:The validated three-dimensional finite element model utilized in this study consisted of 309,583 nodes and 428,760 elements,encompassing anatomical structures such as four vertebral bodies,three intervertebral discs,and various ligaments including the anterior longitudinal ligament,posterior longitudinal ligament,intertransverse ligament,and interspinous ligament.Analysis of the data across seven different motion states revealed no significant deviations from the findings reported by other literature,confirming the accuracy and reliability of the model.The cross-sectional areas of T11-L2 pedicle were 135mm2,154mm2,105mm2,and 139.2mm2,respectively.High stress areas presented within the cancellous bone of the vertebral body,the pedicle and surrounding cortex of the vertebral body during various states of motion according to the stress cloud map analysis.Specifically,the T12 vertebral body exhibited the highest stress level(617.4MPa)under vertical compression,while the T11 vertebral body experienced the highest stress level(200.7MPa)during forward flexion.Additionally,the maximum stress levels recorded for the L1 vertebral body were 314.2MPa,574.4MPa,626.2MPa,641.3MPa,and 527.1MPa during extension,left and right lateral bending,and left and right rotation,respectively.The stress experienced by the L1 vertebral body was found to be minimal in the flexion position and maximal in the left rotation position.T12 vertebral fracture was observed under vertical compression,while T11 vertebral fracture occurred during flexion.L1 vertebral fracture,in combination with ligament injury,was observed during extension,left and right lateral bending,and left and right rotation.High stress areas were identified in anterior longitudinal ligament during extension and left and right lateral bending and in posterior longitudinal ligament during flexion.High stress areas were observed in the intertransverse and interspinous ligaments during movements involving forward flexion,left and right lateral bending,and left and right rotation.Conclusions:In the three-dimensional model of thoracolumbar spine,in-corporating key ligaments,intervertebral discs,and other soft tissue structures,notable areas of high stress were identified within the cancellous bone of vertebral body,pedicle and surrounding cortical bone,and liga-ments.Variations in maximum stress levels were observed in vertebral body under different conditions,result-ing in varying degrees of vertebral body fracture and ligament injury;L1 pedicle exhibited the smallest cross-sectional area and was prone to fracture.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg^-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg^-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.

Objective To analyze the correlation of hepatic steatosis with blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B (CHB). Methods The clinical data of 120 patients with CHB admitted to the hospital from January to December 2021 were retrospectively analyzed. According to the presence or absence of hepatic steatosis, the patients were divided into steatosis group (n=35) and non-steatosis group (n=85). The general clinical data, serological indicators of hepatitis B virus, blood lipid and uric acid levels were compared between the two groups. The correlation of hepatic steatosis grading with blood lipids and uric acid metabolism was analyzed. Results The inflammation and fibrosis degree of liver tissues were significantly different in the two groups (P<0.05). The levels of TG and TC in the steatosis group were higher than those in the non-steatosis group, and the level of HDL-C was lower than that in the non-steatosis group (P<0.05). There was no significant difference between the two groups in LDL-C and uric acid levels (P>0.05). Pearson correlation analysis found that the grade of hepatic steatosis in patients with CHB was negatively correlated with liver tissue inflammation, fibrosis degree and HDL-C level (P<0.05), and positively correlated with TG and TC levels (P<0.05). Conclusion Elderly patients with CHB and hepatic steatosis have abnormal blood lipid metabolism. Hepatic steatosis will exacerbate abnormal blood lipid metabolism but not liver tissue inflammation or fibrosis degree. Clinically, attention should be paid to blood lipid monitoring of elderly patients with CHB.

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

Aim To explore the pro-angiogenesis effect of exosomes derived from human umbilical cord mesenchymal stem cells on cardiac myofibroblasts. Methods The surface markers of hucMSC were detected by flow cytometry. Exosomes were identified by transmission electron microscopy, Nanosight nanoparticle analyzer and Western blot. The effects of exosomes treated cardiac myofibroblasts on endothelial cell proliferation, migration and tubule formation were detected by CCK-8 cell proliferation assay, Transwell assay, cell scratching and endothelial tubule formation assay. The levels of VEGF-A in cardiac myofibroblasts in the control and exosomes-treated group were detected by real-time quantitative PCR etc. After β-catenin/ TCF-mediated transcription inhibitors were added, the expression levels of VEGF-A were detected by Western blot. Results hucMSC did not express CD19, CD34 and CD45, but expressed CD29, CD105 and CD90, which was consistent with the characteristics of mesenchymal stem cells. Exosomes were identified with a particle size of about 100 -200 nm. Compared with hucMSC, exosomes expressed high CD81, low GAPDH, and no Calnexin. Immunofluorescence cytochemical staining revealed that cardiac myofibroblasts expressed α-SMA, and exosomes treated cardiac myofibroblasts promoted endothelial cell proliferation, migration and tubule formation. Further detection showed that the level of VEGF-A in cardiac myofibroblasts increased after exosomes treatment, and the expression level of VEGF-A decreased after β-catenin/ TCF-mediated transcription inhibitor was used. Conclusions Exosomes derived from hucMSC enhance the angiogenesis of cardiac myofibroblasts.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People