A portion of patients undergoing implant restoration require bone augmentation procedures to ensure that there is sufficient bone volume around the implant. For the patients with horizontal bone ridge defects at edentulous sites, with or without mild to moderate vertical bone defects, the shell technique serves as a reliable and minimally invasive bone augmentation method with effective space maintenance. The shell technique involves fixating 1 mm cortical bone blocks to the recipient site, using retention screws and filling the gap between the bone block and recipient bed with particulate bone substitute materials, and covering the barrier membrane to achieve bone augmentation. The overlying tension-free soft tissue closure seals the surgical site while local peripheral blood releases osteoclasts and cytokines that gradually degrade the bone block. The rigid fixation of the bone block ensures a stable internal environment for osteogenesis and a new bone regeneration cycle. Although this technique demonstrates favorable bone augmentation outcomes, it is highly technique-sensitive. There are certain differences in the application scenarios and osteogenic processes for autologous and allogeneic bone shells. The selection of bone blocks and particulate bone substitute materials significantly influences the osteogenic biological process and the predictability of bone augmentation results. Complications associated with the shell technique possess distinct characteristics, such as the immunogenicity of allogeneic bone fragments, soft tissue cracking, and bone fragment loosening. Their prevention and subsequent management substantially impact the success rate of osteogenesis. This article delves into the biological mechanisms of osteogenesis in the bone block technique, summarizing the indications, clinical outcomes, classification of bone blocks, and surgical workflow management, as well as complication prevention and management, aiming to provide a reference for the future application and development of the bone shell technique.

ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg^-1）， medium-dose group （4.86 g·kg^-1）， high-dose group （9.72 g·kg^-1）， and benazepril group （0.01 g·kg^-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

Objective:To investigate the role and analgesic mechanism of ginsenoside Rg1(GRg1)in neuropathic pain in rats.Methods:A total of 30 adult male Sprague-Dawley rats were randomly divided into sham-operation group,spared nerve injury(SNI)group,GRg1 group,GRg1+empty vector group(GRg1+vector group),and GRg1+TLR4 overexpression plasmid group(GRg1+TLR4 group),with 6 rats in each group.The SNI method was used to establish a rat model of neuropathic pain in the latter four groups,and after successful modeling,GRg1 was given by gavage for 14 days,while the plasmid was injected via the caudal vein.The sciatic nerve was exposed for the sham-operation group without any injury manipulation.A mechanical pain threshold detector and a radiation thermal pain threshold detector were used to measure mechanical withdrawal threshold and thermal withdrawal latency on day 1 before surgery and on days 1,3,7,and 14 after surgery.L4-L6 spinal cord tissue samples were collected,and quantitative real-time PCR,Western blot,and indirect immunofluorescence assay were used to measure the mRNA and protein expression levels of GFAP,a marker for astrocyte activation,and Iba-1,a marker for microglial cells;ELISA was used to measure the content of IL-1β,TNF-α,and CXCL1 in spinal cord tissue,and colorimetry was used to mea-sure the content of NO in spinal cord tissue;molecular docking was used to investigate the binding ability and interaction mode between GRg1 and TLR4.Results:GRg1 restored mechanical withdrawal threshold(F=24.67,P=0.000)and thermal withdrawal latency in SNI rats(F=8.058,P=0.034)and downregulated the expression lev-els of GFAP(mRNA:F=37.74,P=0.000;protein:F=98.71,P=0.001)and Iba-1(mRNA:F=62.11,P=0.000;protein:F=187.0,P=0.000)in spinal cord tissues of SNI rats,and it also reduced the levels of IL-1β(F=56.96,P=0.000),TNF-α(F=55.25,P=0.000),CXCL1(F=93.54,P=0.000)and NO(F=30.57,P=0.000)in the spinal cord tissues of SNI rats.The study on mechanisms showed highly stable binding between GRg1 and TLR4,and GRg1 downregulated the expression level of TLR4(mRNA:F=62.66,P=0.000;protein:F=53.52,P=0.000)and the phosphorylation levels of p38(F=300.3,P=0.000)and p65(F=121.6,P=0.000)in spinal cord tis-sues of SNI rats,whereas the overexpression of TLR4 reversed the effect of GRg1(Mechanical Paw Withdrawal Threshold:F=24.67,P=0.000;Thermal Paw Withdrawal Latency:F=8.058,P=0.034;GFAP,mRNA:F=37.74,P=0.009;Protein:F=98.71,P=0.000;Iba-1,mRNA:F=62.11,P=0.006;Protein:F=187.0,P=0.000;IL-1β:F=56.96,P=0.006;TNF-α:F=55.25,P=0.000;CXCL1:F=93.54,P=0.000;NO:F=30.57,P=0.042;TLR4,mRNA:F=62.66,P=0.000;Protein:F=53.52,P=0.000;p38 Phosphorylation Level:F=300.3,P=0.000;p65 Phosphorylation Level:F=121.6,P=0.000).Conclusion:GRg1 may exert an analgesic effect on SNI rats by regulating the TLR4-p38/MAPK-NF-κB signaling pathway and activating the activation of astrocytes and microglial cells in spinal cord tissue.

Objective To investigate the effect of miR-7975 on the malignant phenotype of oral squamous cell carcinoma(OSCC)and its potential mechanisms.Methods This study compared the expression levels of miR-7975 in different oral cell lines by qRT-PCR.miR-7975 mimic and miR-7975 inhibitor were transfected into OSCC cell lines HSC3 and HN4 respectively.Colony formation as-say,CCK8 assay,Transwell assay,and wound healing assay were conducted to evaluate the effects of miR-7975 on the malignant phe-notype of OSCC cells.Western blot was employed to analyze changes in the expression of EMT related proteins and proteins associated with the RAS/ERK signaling pathway.Subcutaneous tumor model of nude mice was used to further validate the tumorigenic effect of miR-7975 in vivo.Results The expression of miR-7975 was downregulated in OSCC cells.Overexpression of miR-7975 reduced the proliferation,migration,and invasion abilities of OSCC cells,whereas downregulation of miR-7975 enhanced these abilities.After miR-7975 overexpression,the expression of the EMT-related protein E-cadherin was upregulated,while N-cadherin,Vimentin,β-catenin,Snail,and Slug were downregulated.Additionally,the expression of proteins related to the RAS/ERK signaling pathway increased.Conversely,the expression of EMT and RAS/ERK signaling pathway-related proteins showed opposite changes when miR-7975 was downregulated.Compared to the control group,the volume and weight of tumors formed in nude mice were significantly smaller after miR-7975 overexpression,while they were significantly larger when miR-7975 expression was reduced.Conclusion miR-7975 exerts its tumor-suppressive effects by inhibiting the proliferation,migration,and invasion of OSCC through the regulation of EMT and the RAS/ERK signaling pathway.

In order to investigate the related pathogens and reveal the etiological characteristics of gout in goslings,191 typical clinical cases from partial regions of China were examined by RT-PCR/PCR detection of viral nucleic acids in domestic poultry and pathological analysis.The autop-sy results show that the clinical cases could be classified into three types based on the severity of urate deposition:severe,moderate,and mild,namely systemic urate deposition,local urate deposi-tion mainly in the liver and kidneys,and only a small amount of fine-grained urate deposition in the liver,gallbladder,or glandular stomach.The results of RT-PCR/PCR detection showed that the to-tal positive rates were as follows:GAstV Group2 63.9％,GAstV Group1 50.3％,AAstV-2 38.7％,novel Muscovy duck parvovirus(NPV)17.8％,GPV 16.2％,GoCV 12.6％,MDPV 7.9％,MDRV 8.4％,DPV 0.5％,GPMV and NDV 0.5％,the AstV-1、ARV、TMUV、NDV、FAdV、GHPyV were zero.Among all the postive samples,the rates of single positive,double positive,and multiple posi-tive were 18.3％,27.2％,and 44.0％,respectively.The rate of single positive samples containing AAstV was only 12.0％,the double or multiple positive samples containing GAstV Group 1/2 was 60.7％,and the rate of samples without GAstV Group 1/2 was 10.5％.The results also showed that 20(10.5％)samples were negative for 16 types of viruses.The AAstV particles isolated from single positive samples appear spherical shape,non-enveloped and 20-80 nm minsize.Two types of virus particles which with spherical shape and diameters of 40-100 and 20-40 nm can be isolated from the negative samples.The virus inoculation results show that the goose embryos can be led to death by clinical GAstV isolates,which with classic histopathological characteristics.Although the GAstV isolates cannot led to death and obvious typical histopathological change in goslings,the vi-ral nucleic acids can be detected in heart,liver,spleen,kidney,intestine and cloacal anal swabs.The above results indicated that there were multiple pathogens co-infection dominated by AAstv in Gosling gout in China,including cross species infections of multiple AAstVs,parvovirus,ARV and suspec-ted novel viruses.Moreover,the GAstV maybe not the only pathogen causing gout in goslings.

Pathological interaction between CD4 + T cells and B cells is one of the important mechanisms of systemic autoimmune diseases. Follicular helper T cells (Tfh) and peripheral helper T cells (Tph) are key cells for assisting B cells. Tph cell is a newly discovered helper T cell subset, and their phenotype is PD-1 highCXCR5 -CD4 +. Tph cell and Tfh cell have certain differences in phenotype, function, and site of action. It interacts with B cells, promoting the differentiation of B cells into plasma cells and the production of autoantibodies, as well as promoting the formation of ELS to maintain local inflammation and antibody responses. Tph cells have recently been reported in various autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren′s syndrome, and IgG4-related diseases. This review summarizes the progress in peripheral immune response of Tph cells in different systemic autoimmune diseases, aiming to explore the new mechanism of autoantibody production and help to develop new diagnostic and therapeutic targets in the future.

Objective:To study the optimal anastomotic angle of end-to-side anastomosis autogenous arteriovenous fistula (AVF).Methods:A case-report and case-series design was used to obtain clinical data on 10 patients with diabetic nephropathy from Department of Nephrology, the 905th Hospital of the Chinese People′s Liberation Army Navy from June 2024 to February 2025. The models of "radial artery-cephalic vein" end-to-side anastomosis in the forearm with anastomotic angles of 30°, 40°and 50°were established. Numerical simulation was used to analyze the blood flow in the model, and to study the effect of different anastomotic angles on blood flow. Wall shear stress (WSS), cross section flow velocity and flow rate, and relative residence time (RRT) were studied in the model. The Whitney test with Holm correction was used to evaluate the difference in the median RRT between the three angle models.Results:At the moment of 0.65 s, the area fraction of low wall shear stress (LWSS) in the 30° model was 7.7%, which was reduced by 2.4% and 3.7% compared to the 40°and 50°models, respectively. At the time of 0.2 s, the area proportions of high wall shear stress (HWSS) in the 30°, 40°and 50°models were 54.4%, 43.9% and 37.4%, respectively. At 0.2 s, the maximum cross section flow velocity reached 4.07, 3.84 and 3.67 m/s for the 30°, 40°and 50°models, respectively. In the cycle, the maximum mean flow velocity for the 30°model reached 1.20 m/s. The mean flow rates of the 30°, 40°and 50°models in the J-5 cross section were 349, 316, and 328 ml/min, respectivly. For patient 6, the area proportions of the RRT>1 region were 11.97%, 14.84% and 15.22% for the 30°, 40°and 50°models, respectively.Conclusions:The optimal anastomotic angle of "radial artery-cephalic vein" for end-to-side anastomosis AVF surgery in patients with diabetic nephropathy is 40°.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged