Chronic neuroinflammation is one of the pathogeneses of Alzheimer's disease(AD),and chemokines and their re-ceptors play a key role in AD pathology.Studies have shown that the expression of CCR3 is increased in AD patients and animal models,and the absence or antagonism of CCR3 can effectively improve the pathological changes of AD animal models and improve the impairment of learning and memory function,which is a potential target for AD treatment.In this review,the research progress of the role of CCR3 and its ligands in the pathogenesis of AD is reviewed,which will provide references for the in-depth disclosure of the pathogenesis of AD and the development of new drugs.

Chronic neuroinflammation is one of the pathogeneses of Alzheimer's disease(AD),and chemokines and their re-ceptors play a key role in AD pathology.Studies have shown that the expression of CCR3 is increased in AD patients and animal models,and the absence or antagonism of CCR3 can effectively improve the pathological changes of AD animal models and improve the impairment of learning and memory function,which is a potential target for AD treatment.In this review,the research progress of the role of CCR3 and its ligands in the pathogenesis of AD is reviewed,which will provide references for the in-depth disclosure of the pathogenesis of AD and the development of new drugs.

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Oligodendrocyte progenitor cells are distributed throughout the central nervous system and can proliferate, migrate and differentiate into oligodendrocytes. The core function of oligodendrocytes is to produce myelin, form a myelin sheath, wrap the axons, and increase the conduction rate of neurons. Recent studies have shown that large numbers of oligodendrocyte progenitor cells exist in the lesions of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease, and these cells play an important role in the repair of neurological damage. The physiological functions of oligodendrocyte progenitor cells and their roles in neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease are reviewed in order to provide a new idea and direction for the research and treatment of neurodegenerative diseases.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective:To explore the surgical method and clinical efficacy of lateral-rectus approach (LRA) in the treatment of fragility fractures of the pelvis (FFP) in the elderly.Methods:A retrospective study was conducted for elderly FFP patients from January 2011 to December 2019. All the pelvic fractures should be exposed and reduced through LRA and fixed with pelvic reconstruction plates and channel screws. Then, a total of 30 elderly patients were included in the study, including 9 males and 21 females, with an average age of 72.5 years (range, 60-87 years). Fractures were caused by car accident in 5 cases, by falling from high places in 8 cases and by tumbling in 17 cases. According to the FFP classification, there were 6 cases of type IIc (6/30, 20%), 22 cases of type III (22/30, 73.33%, of which 13 cases were type IIIa, 7 cases were type IIIb, and 2 cases were type IIIc), 2 cases of type IVa (2/30, 6.67%). Among that, 2 cases suffered ipsilateral acetabular fractures, 17 suffered medical diseases such as hypertension, coronary heart disease, diabetes, etc., and none suffered extremities fractures or other types of injuries. Surgical field was exposed retroperitoneally through LRA, combined with lower limb traction to reduce the anterior and posterior pelvis ring fractures. Then, the reductions were done in direct visions and verified through X-ray fluoroscopy. After that, the posterior ring was fixed with reconstruction plate and/or sacroiliac screws, and the anterior ring was fixed with reconstruction plate or INFIX. The quality of fracture reduction was evaluated by Matta score and the postoperative function was evaluated by Majeed score.Results:All the 30 patients were surgical treated through LRA. The time from injury to operation was 5 to 20 days, with an average of 9.9 days. The operating time ranged from 35 to 150 min (mean, 73.5 min) and the intraoperative bleeding ranged from 220 to 2 400 ml (mean, 586.7 ml). Fractures were successfully reduced under direct vision and the positions of the plates and screws were monitored through X-ray fluoroscopy during the operation. Postoperative X-rays and CT scans showed satisfactory reduction of the pelvic ring. According to Matta criteria, the quality of fracture reduction was evaluated as excellent in 18 cases, good in 6 cases, fair in 4 cases and poor in 2 cases. The overall excellent and good rate was 80% (24/30). All patients were followed up for 6-24 months, the fractures were all healed, and all fractures healed for 2-5 months, with an average of 3.5 months. At the last follow-up, Majeed scores were 86.1±6.11 (range, 66-92), including 21 excellent cases, 7 good cases and 2 fair cases, with an excellent and good rate of 93.3% (28/30). As for complications, 1 patient developed deep venous thrombosis of the affected lower limb, and the thrombosis disappeared after thrombolytic therapy. One patient had fat liquefaction in the incision, and the wound healed after intensive dressing change. After INFIX fixation, 2 patients showed numbness on the lateral thigh of the affected side, and the symptoms were relieved after symptomatic treatment. Four patients were found to have internal fixation screws loosening during follow-up, but still achieved good fracture healing.Conclusion:The entire hemipelvic ring could be exposed through LRA without cutting the peritoneum, so that the sacroiliac joint, ilium wing and anterior ring fractures could be reduced under direct version. In the treatment of pelvis fragility fractures of the elderly, effective reduction and fixation could be achieved using reconstruction plates or channel screws through LRA.

Objective:To investigate the surgical techniques and clinical efficacy of periacetabular osteotomy through the lateral-rectus approach (LRA) for obsolete acetabular fractures.Methods:The 22 patients with old acetabular fracture were retrospectively analyzed who had been admitted to Department of Traumatic Surgery, The Third Affiliated Hospital to Southern Medical University from June 2012 to June 2019. They were 16 males and 6 females, aged from 22 to 61 years (average, 45.0 years). By the Judet-letournel classification, there were 4 anterior + posterior hemitransverse fractures, 2 T-shaped fractures and 16 both column fractures. The time from injury to surgery was 3 to 12 weeks in 15 cases, 3 to 6 months in 5 cases, 9 months in one case, and 3 years in one case. After the whole acetabulum was exposed outside the peritoneum through LRA in all patients, periacetabular osteotomy was conducted under direct vision, followed by fixation with multiple reconstruction plates or integrated acetabular airfoil anatomical plates after reduction. Recorded were the operation time, intraoperative blood loss, fracture reduction quality, affected hip function and complications in the patients.Results:In this cohort the operation time ranged from 110 to 205 min, averaging 140.5 min; intraoperative blood loss ranged from 500 to 2,100 mL, averaging 1,250.4 mL. According to the Matta X-ray criteria, the postoperative reduction was assessed as excellent in 7 cases, as good in 11 and as poor in 4, yielding an excellent and good rate of 81.8% (18/22). All the 22 patients were followed up for 12 to 36 months (mean, 22.1 months) and achieved fracture union. The one-year follow-up showed that their modified Merle d'Aubigné & Postel scores ranged from 6 to 18 points, averaging 14.6 points and giving 6 excellent, 10 good, 3 fair and 2 poor cases [an excellent and good rate of 72.7% (16/22)]. Osteonecrosis of the femoral head developed in 2 patients one of whom underwent total hip replacement.Conclusions:As LRA can expose the entire hemipelic ring from the medial side of the pelvis, the periacetabular osteotomy can be performed and the fractures of anterior or posterior column and the quadrilateral area can be reduced under direct vision through the medial side of the acetabulum. Moreover, ideal results can be achieved with the use of multiple reconstruction plates or integrated acetabular airfoil anatomical plates.

Objective:To investigate the clinical efficacy of lateral-rectus approach(LRA) for vertical shear fracture of pelvis combined with lumbosacral plexus nerve injury.Methods:A retrospective study was conducted of the 37 patients who had been treated at Department of Orthopaedics, The Third Affiliated Hospital to Southern Medical University for vertical shear pelvic fracture combined with lumbosacral plexus nerve injury from August 2010 to August 2018. They were 25 males and 12 females, aged from 18 to 61 years (mean, 36.2 years). By the Tile classification, there were 31 cases of type C1.3, 5 cases of type C2 and one of type C3. LRA was used in all the patients to explore and release the lumbosacral plexus nerve and to reduce the sacral fracture. The posterior ring was fixated with an anterior iliac plate or sacral screws before fixation of the anterior ring and treatment of the acetabular fracture. The operation time, intraoperative bleeding volume, quality of fracture reduction, fracture union time and recovery of nerve and muscle strength were recorded.Results:For this cohort, the operation time ranged from 105 to 228 minutes (mean, 155.0 minutes) and the intraoperative bleeding volume from 680 to 2, 440 mL (mean, 1, 070 mL). Thefollow-up time ranged from 1 to 8 years (average, 2 years). According to the Matta criteria, the quality of fracture reduction was evaluated as excellent in 21 cases, as good in 12 cases and as fair in 4 cases, giving an excellent and good rate of 89.2%. Follow-ups revealed reduction loss in 4 patients, nonunion and reduction loss in one patient and bony union in the other 32 patients after 8 to 12 weeks (mean, 10.1 weeks). According to the criteria by the Nerve Injuries Committee of the British Medical Research Council (BMRC), the recovery of nerve and muscle strength achieved M5 (full recovery of neurological symptoms) in 22 cases, M4 (fine recovery of neurological symptoms) in 7 cases, M1, M2 and M3 (partial recovery of neurological symptoms) in 5 cases, and M0 (no recovery of neurological symptoms) in 3 cases.Conclusion:LRA is an ideal surgical approach for treatment of pelvic vertical shear fractures complicated with lumbosacral plexus nerve injury, because it can well expose the medial pelvic joint from the sacroiliac joint to the symphysis pubis, allow direct release of the lumbosacral plexus nerve compressed and stretched, and, together with traction of the lower limbs, lead to satisfactory fracture reduction.

Objective:Numerous studies have shown that neuroplasticity plays an important role in the pathogenesis of depression. This study aimed to investigate the relationship between the brain derived neurotrophic factor (BDNF) (Val66Met, rs6265) genotype and gray matter volume (GMV) in the first episode and treatment-naive patients with major depressive disorder (MDD) and healthy subjects.Methods:This study included 41 first episode and treatment-naive MDD patients (MDD group) and 44 sex and age matched healthy controls (HC group). All participants were arranged to take magnetic resonance imaging (MRI) scan. Meanwhile, BDNF rs6265 polymorphism was detected. Voxel-based morphometry (VBM) method was then performed to test the impact of the diagnosis (MDD vs. HC) and BDNF genotype (Met allele vs. Val/Val homozygous) on GMV. Results:There was no statistically significant difference on BDNF rs 6265 sites alleles frequency and genotype between MDD and HC groups (MDD χ 2=0.004, P>0.05; HC χ2=0.048, P>0.05). Gray matter volume in the left precuneus ( F=3.702, P<0.001), right middle temporal gyrus ( F=4.020, P<0.001) and cerebellum vermis_4_5 ( F=3.836, P<0.001) was larger in MDD patients than in the control group. BDNF genotype had effects on left fusiform gyrus ( F=-4.152, P<0.001). BDNF genotype-diagnosis interaction was found to be associated with left anterior cingulate cortex ( F=-4.775, P<0.001) and right anterior cingulate ( F=-3.795, P<0.001). For participants with Val/Val homozygous, compared to HC group, the volume of left anterior cingulate was reduced in MDD patients ( F=-3.729, P<0.001). For participants with the Met allele, compared to healthy controls, MDD patients showed significantly increased GMV in the left middle frontal gyrus ( F=4.317, P<0.001), right inferior occipital gyrus ( F=4.744, P<0.001), right supramarginal gyrus ( F=3.838, P<0.001), and left median cingulate gyrus( F=4.041, P<0.001). Separately in MDD patients and the control group, the GMV did not differ between the Val/Val homozygous group and the Met allele group. Conclusion:BDNF rs6265 alleles could be related to brain structural abnormalities in MDD patients, and could further explain the pathological mechanism of MDD.