Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals ; Spinal Cord Injuries/physiopathology* ; Demyelinating Diseases/etiology* ; Remyelination/physiology* ; Macaca fascicularis ; Disease Models, Animal ; Myelin Sheath/pathology* ; Oligodendroglia/pathology* ; Schwann Cells/pathology* ; Female ; Spinal Cord/pathology* ; Axons/pathology*

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective To explore the presentation of T2 weighted magnetic resonance imaging(T2WI)and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters in patients with prostate cancer and their correlations with prostate specific antigen(PSA)level and International Society of Urological pathology(ISUP)grading.Methods A total of 82 patients with prostate diseases who were admitted to Yixing Traditional Chinese Medicine Hospital between March 2019 and June 2023 were selected as research objects,including 52 patients with prostate cancer and 30 patients with benign prostatic hyperplasia.T2WI and DCE-MRI parameters of these patients were compared.Results The proportion of prostate cancer patients with T2WI score≥4 was 50.00%,which was higher than that of the benign prostatic hyperplasia patients(P<0.05).The peak time(Tmax)of prostate cancer patients was 70 541.44(45 035.20,90 655.41)ms,which was shorter than that of the patients with benign prostatic hyperplasia(P<0.05).The fastest enhancement rate(Rmax)of prostate cancer patients was 36.60±14.41,which was higher than that in patients with benign prostatic hyperplasia(P<0.05).The proportions of patients with T2WI score≥4 in stages Ⅲ-Ⅳ,ISUP grading≥4,and PSA≥50 ng/ml were 62.50%,75.00%and 63.16%,respectively,which were significantly higher than those in stages Ⅰ-Ⅱ,ISUP grading≤3,and PSA level<50 ng/ml(all P<0.05).The Tmax of patients in stages Ⅲ-Ⅳ was 68 405.44(43 506.43,82 204.32)ms,which was lower than that of stagesⅠ-Ⅱpatients(all P<0.05).The Rmax of patients in stages Ⅲ-Ⅳ was 39.16±9.50,which was higher than that of stages Ⅰ-Ⅱ patients(all P<0.05).The Tmax of patients with ISUP grading≥4 was 66 504.32(43 506.43,84 053.12)ms,which was lower than that of patients with ISUP grading≤3(P<0.05).The Rmax of patients with ISUP grading≥4 was 40.38±9.75,which was higher than that of patients with ISUP grading≤3(P<0.05).The Tmax of patients with PSA≥50 ng/ml was 63 044.22(45 035.20,82 204.32)ms,which was shorter than that of patients with PSA<50 ng/ml(P<0.05).The Rmax of patients with PSA≥50 ng/ml was 39.15±9.05,which was higher than that of patients with PSA<50 ng/ml(P<0.05).Tmax was negatively correlated with PSA(P<0.05),while Rmax was positively correlated with PSA(P<0.05).T2WI manifestations and Rmax were positively correlated with ISUP grading(all P<0.05),while Tmax was negatively correlated with ISUP grading(P<0.05).Conclusion T2WI and DCE-MRI parameters are correlated with clinical staging,ISUP grading,and PSA level of prostate cancer,which is worthy of further clinical research.

Malignant mesothelioma(MMe)is a malignant tumor originating from mesothelial tissues,occurring mostly in locations like pleura,pericardium and peritoneum.The extensive research on its treatment has been car-ried on as tackling to the challenge of poor prognosis of the disease.Conventional treatment modalities including sur-gery,chemotherapy and radiotherapy all exhibit limited efficacy,resulting in persistently low survival rates.Hence,exploring novel therapeutic approaches is paramount for improving the prognosis of mesothelioma patients.Targeted therapy and immunotherapy,as emerging cancer treatment modalities,exert their effects by targeting specific mo-lecular markers on tumor cells or immune cells,thus inhibiting tumor growth and metastasis,thereby offering new hope for mesothelioma treatment.This article provides a comprehensive review of recent research progress in targeted therapy and immunotherapy for mesothelioma.

Objective To evaluate the performance of the Quality of Life Instrument for Chronic Dis-ease Nephrotic Syndrome [QLICD-NS(V2.0)] in patients with nephrotic syndrome.Methods A total of 203 patients with nephrotic syndrome (NS) diagnosed in the Department of Nephrology,Affiliated Hospital of Guangdong Medical University from March 2021 to November 2021 were selected for QLICD-NS(V2.0) eval-uation,and the evaluation methods were generalization theory (GT) and item response theory (IRT).The dif-ficulty,discrimination coefficient and information amount of each item were obtained by using Multilog 7.0 software to analyze the grade response model (GRM) of IRT.Results The results of GT showed that the contribution ratio of the global total score in the four domains of QLICD-NS(V2.0) scale was evenly distribu-ted,and the generalization coefficient of the four domains was greater than 0.50.Except for social function,the variance component of the participants in the other three domains were greater than the item variance compo-nent,and the reliability index of each domain was greater than 0.50.The results of IRT showed that the dis-crimination degree of QLICD-NS(V2.0) scale was 0.82.Except for items TNS7 and TNS8,the difficulty coef-ficients of the other items ranged from -3 to 3 and increase monotonically.Conclusion The QLICD-NS (V2.0) scale has good reliability in physiological function and psychological function,and is acceptable in so-cial field and special function.The QLICD-NS(V2.0) scale developed in this study has good performance.

Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

Objective:To investigate the effects of preoperative pre-rehabilitation on early functional recovery after knee arthroplasty under the multidisciplinary collaboration mode of accelerated rehabilitation surgery.Methods:The clinical data of 51 patients who underwent total knee arthroplasty in the Department of Orthopedics, Jinjiang Hospital from September 2019 to December 2021 were retrospectively analyzed. These patients were divided into an observation group ( n = 24) and a control group ( n = 27). The observation group received pre-rehabilitation before knee replacement surgery, while the control group did not. After completing the admission procedures, patients in the observation group underwent rehabilitation evaluation in the rehabilitation clinic and received individualized rehabilitation training. The control group did not undergo preoperative pre-rehabilitation but underwent the same individualized rehabilitation training as the observation group. The rehabilitation specialist evaluated the patients' rehabilitation scores [hospital for special surgery knee (HSS) score, visual analog scale (VAS) score] at 2 and 5 days after surgery. The main outcome measures included the range of motion (ROM) of the patient's knee joint at 2 and 5 days after surgery, HSS score at 2 and 5 days after surgery, VAS score at 5 days after surgery, the number of days from surgery to discharge, the incidence of postoperative complications, and the rate of outpatient visits after surgery. Results:There was no significant difference in postoperative ROM of the knee joint between the observation and control groups at 2 days after surgery ( P > 0.05). However, there was a significant difference in score of ROM of the knee joint at 5 days after surgery between the two groups [(100.08 ± 7.75) points vs. (88.44 ± 16.09) points, t = 3.34, P = 0.002]. There was no significant difference in HSS score between the two groups at 2 days after surgery ( P > 0.05). However, there was a significant difference in HSS score between the two groups at 5 days after surgery [(62.84 ± 5.78) points vs. (57.09 ± 6.53) points, t = 3.31, P = 0.002]. There was a significant difference in VAS score (exercise) between the two groups at 5 days after surgery [(3.42 ± 1.02) points vs. (5.37 ± 1.15) points, t = -6.39, P < 0.001]. There was no significant difference in the number of days from surgery to discharge between the two groups ( P > 0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P > 0.05). However, there was a significant difference in the rate of outpatient visits between the two groups [7/17 vs. 1/26, χ2 = 4.45, P = 0.035]. Conclusion:Preoperative pre-rehabilitation in the accelerated rehabilitation surgery model under multidisciplinary collaboration can help improve the early function of patients undergoing total knee arthroplasty, reduce the pain of postoperative rehabilitation, improve the postoperative rehabilitation compliance, and ultimately enhance patient satisfaction with the surgery.

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals ; Mice ; Male ; Cell Line ; Rats ; Kidney/physiology* ; Fibrosis/drug therapy* ; Renal Insufficiency, Chronic/drug therapy* ; Adenine ; Epithelial-Mesenchymal Transition ; Aquaporin 1/metabolism*