Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

Diabetic cardiomyopathy （DCM）， a cardiovascular complication caused by diabetes mellitus， is a major cause of heart failure and even sudden cardiac death in diabetic patients. Traditional Chinese medicine （TCM） posits that the core pathogenesis of DCM lies in internal deficiency and superficial excess， characterized by deficiency of both Qi and Yin combined with phlegm and blood stasis. Modern medical treatments for DCM primarily focus on blood glucose control and symptom alleviation yet lack targeted therapeutic strategies. In contrast， TCM offers a wealth of practical experience and a complete theoretical system， demonstrating definite clinical efficacy and high medication safety in DCM management. As a classic formula for tonifying Qi and nourishing Yin， Shengmaisan comprises Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. It contains multiple bioactive components， including ginsenosides， ophiopogonin， schisandrins， and homoisoflavonoids， which exhibit cardioprotective properties. The therapeutic mechanisms of Shengmaisan-like formulae for DCM involve enhancing myocardial contractility， attenuating myocardial fibrosis， modulating mitochondrial quality control， regulating glucose metabolism， mitigating oxidative stress， and suppressing inflammatory responses. Clinically， Shengmaisan-like formulae not only manage hyperglycemic status but also ameliorate cardiac structural and functional impairments and enhance exercise tolerance in DCM patients， playing a vital role in the prevention， treatment， and rehabilitation of DCM. This paper analyzes the feasibility of Shengmaisan-like formulae in DCM management and synthesizes current research achievements regarding their chemical components， mechanisms of action， and clinical applications， aiming to provide a scientific foundation for the use of such formulae in the treatment of DCM.

The number of patients with eye diseases in China is enormous,and the negative effects of these conditions,such as impaired visual function,psychological burdens,and restricted social participation,are becoming increasingly severe.Due to the limited and unevenly distributed ophthalmic resources,and the significant limitations of traditional diagnostic and therapeutic approaches in terms of accuracy and efficiency,there is an urgent need for more sensitive and efficient modalities.With the rapid advancement of artificial intelligence technology,ophthalmic diagnosis has entered a new stage of intelligent transformation.Facial photos,as a noninvasive and convenient medium,show unique advantages in eye disease diagnosis.Artificial intelligence systems based on facial photo analysis have been applied to the screening and diagnosis of conditions such as myopia,strabismus,ptosis,and thyroid eye disease,showing promising results.This review introduces the workflow of intelligent diagnosis for ocular diseases based on facial photographs,with a focus on recapitulating relevant research findings both domestically and internationally in recent years.It summarizes the innovative features and application advantages of intelligent diagnosis systems for eye diseases based on facial photos,analyzes the current technical bottlenecks and challenges in application,proposes corresponding countermeasures,and discusses future development directions,aiming to provide references and new insights for the intelligent screening and diagnosis of eye diseases.

The number of patients with eye diseases in China is enormous,and the negative effects of these conditions,such as impaired visual function,psychological burdens,and restricted social participation,are becoming increasingly severe.Due to the limited and unevenly distributed ophthalmic resources,and the significant limitations of traditional diagnostic and therapeutic approaches in terms of accuracy and efficiency,there is an urgent need for more sensitive and efficient modalities.With the rapid advancement of artificial intelligence technology,ophthalmic diagnosis has entered a new stage of intelligent transformation.Facial photos,as a noninvasive and convenient medium,show unique advantages in eye disease diagnosis.Artificial intelligence systems based on facial photo analysis have been applied to the screening and diagnosis of conditions such as myopia,strabismus,ptosis,and thyroid eye disease,showing promising results.This review introduces the workflow of intelligent diagnosis for ocular diseases based on facial photographs,with a focus on recapitulating relevant research findings both domestically and internationally in recent years.It summarizes the innovative features and application advantages of intelligent diagnosis systems for eye diseases based on facial photos,analyzes the current technical bottlenecks and challenges in application,proposes corresponding countermeasures,and discusses future development directions,aiming to provide references and new insights for the intelligent screening and diagnosis of eye diseases.

Objective:To retrospectively analyze clinical efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) in southern Zhejiang, China.Methods:A retrospective observational study was conducted on CU patients who received omalizumab treatment at the First Affiliated Hospital of Wenzhou Medical University from January 1st, 2018 to August 1st, 2021. Through the outpatient follow-up visits, the disease activity, condition control, and quality of life were evaluated using the 7-day urticaria activity score (UAS7) , urticaria control test (UCT) , and dermatology life quality index (DLQI) . In addition, changes in disease condition, recurrence after withdrawal, and adverse events were assessed. Independent-sample t test was used for intergroup comparisons of normally distributed measurement data, Wilcoxon signed-rank sum test or Kruskal-Wallis H test was used for comparisons of non-normally distributed measurement data, and chi-square test or Fisher′s exact test was used for comparisons of enumeration data. Results:A total of 252 CU patients with poor response to antihistamines were included, with a baseline UCT score of 5.0 ± 2.4 points, a UAS7 score of 25.6 ± 6.2 points, and a DLQI score of 17.5 ± 4.7 points; among them, 204 (81.0%) were treated with omalizumab at an initial dose of 300 mg, and 48 (19.0%) with omalizumab at an initial dose of 150 mg. At the end points (12.0 ± 1.4 months after the start of treatment) , an overall control rate of 90.3% (224/248) was achieved after the omalizumab treatment; concretely, 137 (55.2%) patients achieved complete control (UCT = 16 points) , 87 (35.1%) achieved partial control (12 points ≤ UCT < 16 points) , and 24 (9.7%) showed no response (UCT < 12 points) , while 10 with partial response shifted to complete control after dose increase. During the treatment period, recurrence occurred in 50 patients (36.5%) , of whom 32 patients opted for retreatment with omalizumab, and then 30 (93.8%) achieved partial or complete control. Adverse events were reported in 8 patients (3.2%) , and all were mild or moderate.Conclusion:Omalizumab was effective in the real-world treatment of CU, and could improve patients′ quality of life, with a favorable safety profile.

OBJECTIVE：To obs erve the protective effect of protoca techuic aldehyde（PAL）on neurovascular unit （NVU） homeostasis damage in rats after cerebral ischemia-reperfusion injury （CIRI）. METHODS ：SD rats were randomly divided into sham operation group ，model group ，PAL high-dose and low-dose groups （10，20 mg/kg），with 11 rats in each group. Administration groups were given relevant medicine intragastrically. Sham operation group and model group were given the same volume of normal saline intragastrically ，10 mL/kg once a day ，for 5 days. After last administration ，CIRI model was induced by suture method ；the ultrastructural changes of NVU were observed by transmission electron microscope. Western blot assay was used to detect the expression of NUV related proteins （MAP-2，GFAP，AQP-4）in cerebral tissue. Immunofluorescence staining was used to observe the positive expression of above proteins in cerebral cortex. RESULTS ：Compared with sham operation group ， blood-brain barrier （BBB）structure of model group was destroyed severely ，the vascular lumen became narrower ，lateral edema of endothelial cells was severe ，and the thickness of basement membrane varied ；the nuclei of neurons were pyknosis and there was a large area of edema in the surrounding tissues ；the structure of glial cells was seriously damaged ，the cell body was shrunk and organelles were lost ；protein expression （or positive expression ）of MAP- 2 in brain tissue （or cerebral cortex ）were significantly decreased （P＜0.05 or P＜0.01），while protein expression （or positive expression ） of GFAP and AQP- 4 were increased significantly（P＜0.01）. After PAL intervention ，the rats had less BBB damage ，and the morphology of vascular lumen and basement membrane were not completely destroyed ；the damage of neurons was alleviated ，the pyknosis of neurons was decreased ， the chromatin was homogeneous and the heterochromatin was decreased；the damage of glial cell structure was alleviated protein expression of GFAP and AQP- 4（except for low-dose group） in cerebral tissue and positive expression of MAP- 2 and GFAP protein in cerebral cortex were reversed @qq.com significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：PAL can protect the stability of NVU from damage in CIRI model rats； the mechanism may be related to up-regulating the expression of MAP- 2 protein in cerebral cortex and down-regulating the expression of GFAP and AQP- 4 protein in brain tissue.

Objective: To analyze the risk factors of implant-related complications in adult patients with adult degenerative scoliosis (ADS) who underwent long-level internal fixation. Methods: This was a retrospective study that analyzed 99 cases of adult degeneration scoliosis patients who underwent long level posterior pedicle screw fixation in our hospital between June 2013 and January 2016. The internal fixation and related complications were evaluated by measuring and analyzing the radiographic data of the postoperative X-ray films. The timepoints of measurement were pre-operation, before discharge, half a year, 1 year, when complications occur and the final follow-up after operation. Implant-related complications included proximal junctional kyphosis (PJK), proximal junctional failure (PJF), distal junctional kyphosis/failure (DJK/DJF), rod breakage in addition to other radiographic implant-related complications (that were not related to PJF) such as screw loosening, breakage or pullout, or interbody graft and hook or set screw dislodgements seen on follow-up radiographs. The incidence of postoperative implant-related complications was counted. All the cases included in the study were divided into the complication group and the non-complication group. Statistical difference between groups at different follow-up time point was analyzed. Potential risk factors were identified using univariate testing. Multivariate Logistics regression was used to analyze the independent risk factors for implant-related complications. The postoperative functional scores were assessed using the Oswestry Disability Index (ODI), Japanese Orthopaedic Association Scores (JOA), Visual Analogue Scale (VAS), and Lumbar Stiffness Disability Index (LSDI). Functional scores were tested using group t tests. Patients were divided into groups according to PI-LL <10 °, 10°-20 ° and > 20 °. The preoperative and postoperative radiographical parameters and clinical function score among each groupwere compared.The best PI-LL matching value was verified by analyzing the effect of long-segment fusion orthopedics on ADS. Results: Ninety-nine ADS patients who underwent long level posterior fixation were included. The incidence of patients with mechanical complications was 30.3%. Univariate analysis showed that chronic risk factors of postoperative implant-related complications after surgery of ASD included diabetes (OR=3.52, P=0.001) and blood transfusion (OR=2.61, P=0.030); surgical risk factor isosteotomy (OR=4.33, P=0.000); preoperative imaging risk factor was preoperative SVA (OR=1.03, P=0.000); the risk factors for increased risk of the implant-related complications included anemia (OR=1.17, P=0.810), cardiac complications (OR=1.80, P=0.290) and hospital stay (OR=1.11, P=0.110). Independent predictors identified on multivariate Logistics regression modeling included osteotomy (OR=3.05, P=0.032), and preoperative SVA (OR=1.03, P=0.007). The radiographical parameters and clinical function scores of the PI-LL 10°-20° group were better than or partially superior to those of the PI-LL<10° group and the PI-LL>20° group. The postoperative SVA of the PI-LL 10°-20° group was significantly lower than that of the PI-LL<10° group (t=2.399, P=0.020) and the PI-LL>20° group (t=-3.074, P=0.005). The incidence of implant-related complications in the PI-LL 10°-20° group was significantly lower than that in the PI-LL<10° group (t=1.584, P=0.003). Survival analysis showed that the PI-LL 10°-20° group was significantly better than the PI-LL<10° group (χ²=7.782, P=0.005), while the PI-LL 10°-20° group had better survival than PI-LL>20° group, althoughthatwas not statistically significant (χ²=2.542, P=0.111). Conclusion Risk factors of postoperative implant-related complications after surgery of ASD included osteotomy and preoperative SVA. Patients with one or more of these risk factors should be informed of the risk increase with informed consent. Patients with PI-LL between 10 ° and 20 ° had better postoperative radiographical parameters and clinical functional scores. They should be optimized preoperatively and followed up closely during the postoperative period.

Objective To evaluate the role of C-X-C chemokine receptor type 4 ( CXCR4) in the dorsal root ganglia ( DRG) in incisional pain in rats. Methods Thirty-two male Sprague-Dawley rats, aged 7-10 weeks, weighing 250-300 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups (n＝8 each) using a random number table method: sham operation group (group S), CXCR4 antagonist AMD3100 plus sham operation group (group A+S), incisional pain group (group I) and CXCR4 antagonist AMD3100 plus incisional pain group (group A+I). Rats were anesthetized with sevoflu-rane. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and no incision was made 30 min later in group A+S. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the left hindpaw in group I. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and 30 min later the model of incisional pain was established in group A+I. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before surgery and 2, 4, 8, 16 and 24 h after surgery. The rats were sacrificed after the last measurement of pain threshold and the DRGs of the lumbar segment (L4-6) were removed for detecting the expression of CXCR4, phosphorylated extracellular regulated protein kinase ( p-ERK) and total ERK ( t-ERK) by Western blot. Results Compared with group S, MWT was significantly decreased and TWL was shortened at T1-5in group I and group A+I, and the expression of CXCR4 and p-ERK in DRGs was significantly up-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group I, no significant change was found in the expression of CXCR4, p-ERK and t-ERK in group A+I, and no significant change was found in the parameters mentioned above in group A+S (P＞0. 05). Compared with group I, MWT was significantly increased and TWL was prolonged at T1-5, the expression of CXCR4 and p-ERK in DRGs was down-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group A+I (P＞0. 05). Conclusion CXCR4 in DRGs is involved in incisional pain, and the mechanism may be re-lated to activating ERK1∕2 signaling pathway in rats.

Objective To investigate the incidence of fatigue in maintenance hemodialysis(MHD)patients and its related factors.Methods A total of 289 patients on MHD between January 2016 and March 2017 in hemodialysis centers of the First Affiliated Hospital of Xinjiang Medical University,Xinjiang Yili Kazak Autonomous Prefecture Friendship Hospital,and Yili Prefecture Hospital were enrolled.Internationally standard fatigue rating scale(FAI)was applied to assess the incidence of fatigue in MHD patients,and subjective comprehensive nutrition assessment(SGA)protein energy wasting rating scale was used to assess protein energy wasting(PEW)conditions.All patients were divided into the fatigue group and the non-fatigue group according to the FAI score.The clinical data and the blood biochemical indicators in two groups were compared.The risk factors of fatigue in MHD patients were analyzed by logistic regression method.Results The incidence of fatigue was 83.0％in MHD patients,and the rate of PEW was 62.6％.Blood total cholesterol in the fatigue group was lower than that of the non-fatigue group(P ＜ 0.05).The difference between SGA scores of two groups had statistical significance(P ＜ 0.001).Single factor logistic regression analysis results showed that higher SGA score(OR=1.312,95％CI:1.163-1.481,P ＜ 0.001),lower blood total cholesterol(OR=0.661,95％CI:0.496-0.880,P=0.005)were risk factors of fatigue in MHD patients.Multivariable logistic regression analysis results showed that higher SGA score(OR=5.286,95％CI:2.078-13.442,P ＜ 0.001)was an independent risk factor of fatigue in MHD patients.Conclusions The incidence of fatigue and PEW are high in MHD patients.PEW is an independent risk factor of fatigue in MHD patients.

OBJECTIVE To investigate the transgenerational effect of neuroendocrine metabolic programmed alteration in adult intrauterine growth retardation (lUGR) offspring rats with prenatal nicotine exposure. METHODS Pregnant Wistar rats were administered daily with nicotine (2 mg.kg-1 ) by sc from gestational day 11 until delivery. F1 offspring was fed with a standard diet before four groups in F2 were set up according to the cross-mating between F1 normal adult rats and nicotine-induced lUGR adult rats. CC group was mated by F1 normal adult rats, CN group by F1 normal adult male rats and lUGR adult female rats, NC group by F1 lUGR adult male rats and normal adult female rats, while NN group was mated by F1 lUGR adult rats. F2 adult rats were subjected to a fortnight ice water swimming stimulus. Blood samples were collected before and after stress and then detected for the levels of adrenocortico-tropic hormone ( ACTH), corticosterone ( CORT), glucose, triglycerides ( TG) and total cholesterol (TCH). RESULTS Before stress, the level of serum CORT in F2 male rats of NN group was decreased to 73.9% of that of the CC group (P<0.05),while the level of serum TG in F2 male rats of CN and NC groups was increased to 1.43 and 1.52 times that of the CC group, respectively ( P<0.05). Meanwhile, the level of serum TG in F2 female rats of CN, NC and NN groups was increased to 1.71, 1.80 and 1.81 times that of the CC group, respectively (P<0.05). After stress, the serum CORT gain rate in F2 male rats of CC group was -1.67%, but was 36.0% in NN group. The serum glucose level in male NC group and in female CN group was increased to 1.61 and 1.62 times that of the corresponded CC groups, respectively (P<0.01). Furthermore, the serum TG gain rate in F2 rats of each nicotine group was decreased markedly in comparison with their corresponding controls (P<0.05), ie, the serum TG gain rates in F2 male rats of CN, NC and NN groups were decreased to 46.4%, 16.7% and 7.7% of the CC group, while the serum TG gain rates in F2 female rats of these groups were decreased to 20.6%, 4.0% and 8.4% of the CC group, respectively. Compared with CC group, TCH level of females and males in NN group was decreased by 40.5% and 21.9%(P<0.01) before stress, respectively, and the TCH gain rate of females in NN group was increased by 49.7%(P<0.05) after stress. CONCLUSION The reproductive and developmental toxicities and the neuroendocrine metabolic programming alterations induced by prenatal nicotine exposure are transgenerated to F2 offspring and these effects exhibit gender and parental differences.