BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

Objective:To investigate the clinicopathological characteristics of dedifferentiated endometrial carcinoma/undifferentiated endometrial carcinoma (DDEC/UDEC) with loss of expression of SMARCA4.Methods:A total of 10 cases with loss of expression of SMARCA4 were diagnosed at Fujian Cancer Hospital between January 2019 and December 2023. A retrospective analysis was conducted on the clinical characteristics, morphology, immunophenotype, molecular classification, and prognosis.Results:(1) Clinical characteristics: among 10 cases of DDEC/UDEC with loss of expression of SMARCA4, the patients′ age ranged from 48 to 65 years, with a median age of 56 years.Five cases were classified as International Federation of Gynecology and Obstetrics (FIGO) stages Ⅰ-Ⅱ, while the remaining five were categorized as stages Ⅲ-Ⅳ. (2) Pathological features: tumor cells exhibited poor cell adhesion, with common intravascular tumor emboli (8/10), occasional vacuolated nuclei (6/10), rhabdoid cells (4/10), and starry sky phenomenon formed by tissue cell phagocytosis apoptosis bodies or fragments (4/10). Six cases (6/10) showed loss of mismatch repair (MMR) protein expression, two cases (2/10) exhibited p53 mutant expression, and five cases (5/10) tested positive for programmed cell death ligand 1 (PD-L1). (3) Molecular subtyping: molecular subtyping revealed POLEmut in 1 case (1/10), mismatch repair deficient (MMR-d) in 5 cases (5/10), p53 abn in 1 case (1/10), and no specific molecular profile (NSMP) in 3 cases (3/10). (4) Prognosis: the follow-up period ranged from 7 to 42 months, with a median of 20 months. Five patients succumbed to the tumor, whereas the remaining five exhibited no recurrence during subsequent postoperative evaluations. The 2-year progression-free survival rates and overall survival rates were 58.3% and 52.5%, respectively.Conclusions:Loss of expression of SMARCA4 occurs in approximately 1/5 of DDEC/UDEC, which presents with an aggressive clinical course and a poor prognosis. About half of them show MMR protein loss expression and PD-L1 positive expression, suggesting that there might be benefit from treatment with immune checkpoint inhibitors.

Objective:To explore the predictive value of deep learning (DL)-based coronary artery calcification score (CACS) for obstructive coronary artery disease (CAD) and noncalcified plaque/mixed plaque in type 2 diabetes mellitus (T2DM).Methods:Forty hundred and twenty-four consecutive T2DM patients who accepted CACS scan and coronary CT angiography (CCTA) from December 2012 to December 2019 were included retrospectively, with clinical risk factors and plaque features collected. Plaque composition was classified as calcified, non-calcified or mixed plaque. Obstructive CAD was defined as maximum diameter stenosis≥50%. CACS was calculated with a fully automated method based on DL. Univariate and multivariate logistic regressions were applied to select statistically significant factors and the odds ratios(ORs) were measured. Receiver operating characteristic (ROC) curve was evaluated to assess the predictive performance.Results:Increased CACS was associated with a significantly higher odds of obstructive CAD in CCTA (adjusted ORs were 2.22, 6.18 and 16.98 for CACS=1-99, 100-299, 300-999 vs. CACS=0, and P values were 0.009,<0.001,<0.001 respectively). The area under ROC curve (AUC) of CACS to predict obstructive CAD was 0.764. Compared with 0, increased CACS was associated with increased risk of non-calcified/mixed plaque (adjusted ORs were 2.75, 4.76, 5.29 for CACS=1-99, 100-299, 300-999 respectively and P values were 0.001,<0.001,<0.001 respectively). The AUC of CACS to predict non-calcified/mixed plaque was 0.688. It took 1.17 min to perform automated measurement of CACS based on DL in total, which was significantly less than manual measurement of 1.73 min ( P<0.001). Conclusion:DL-based CACS can predict obstructive CAD and non-calcified plaque/mixed plaque in T2DM, which is economical and efficient, and has important value for clinical diagnosis and treatment.

Objective:Through TTC staining, immunohistochemical analysis, RT-PCR and hind limb motor function evaluation and other experimental methods, to explore the regulatory mechanism of metformin on anti-apoptosis in rats with spinal cord injury (SCI).Methods:Establish a rat spinal cord injury model. Through Basso-Beattie -Bresnahan locomotor rating scale (BBB) and cant test to evaluate the recovery of hindlimb motor function in rats. The changes of necrotic area of spinal cord tissue were compared by TTC staining. Extraction of rat spinal cord tissue, by Dot blot analysis and immunohistochemical detection of the hydroxyl of DNA methylation level. By qPCR, Western Blot detection TET2mRNA and protein expression level, and the changes in the scope of spinal cord injury were detected by inhibiting the expression of TET2. The interaction between TET2 and Foxo3a was detected by immunoblotting and immunoprecipitation. Through RT-PCR assay Foxo3a downstream related changes in the level of gene expression.Results:Compared with the SCI+NS group, the necrotic area of the spinal cord tissue was reduced after metformin treatment, and the BBB score and the incline test score were higher ( P<0.05). At the same time, we found that the levels of TET2mRNA and protein increased significantly after SCI at 24 h, and the 5-hmC level of DNA increased. The levels of TET2mRNA and protein and 5-hmC increased further after the use of metformin. After using SC-1, compared with the SCI+MET group, the level of 5-hmC decreased and the area of infarction increased. After SCI, the mRNA levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the mRNA levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). After SCI, the 5-hmC levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the 5-hmC levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). Conclusion:Metformin can promote the interaction between TET2 and Foxo3a, increase the 5-hmC level of the overall DNA, and inhibit the activation of related apoptosis genes, thereby improving tissue damage and nerve function recovery after spinal cord injury.

OBJECTIVE: To construct a three-dimensional (3D) finite element mechanical model of total hip arthroplasty for comparison of biomechanical differences of the hip joint following capsule repair and postoperative rehabilitation. METHODS: Six frozen specimens of hip joint posterior capsule ligament complex were collected in a bone-capsule-bone manner, and the load-strain curve and other mechanical properties of the specimens were tested using a universal material testing machine. Thin-section CT data of the pelvis and lower limbs obtained from a volunteer were imported into Mimics software to construct a 3D model of the hip joint. Digital models of the cup, femoral prosthesis and joint capsule were created in CATIA software and imported into Mimics to simulate total hip arthroplasty; the assembled data were imported into ABAQUS software. The properties of the capsule were set according to results of the mechanical test, anatomical studies, and constitutive equations, and the biomechanics of the anatomically repaired and conventionally repaired capsules were compared during hip flexion. RESULTS: The results of testing on the 6 capsule specimens showed a mean ultimate tensile strain of (39.21±5.23)% and a mean of ultimate tensile strength of 1.65±0.38 MPa. The stress-strain curve of the finite element model was consistent with the results of mechanical test on the specimens and the biochemical characteristics of the capsule. The stress was distributed evenly in the anatomically repaired capsule during hip flexion but not in the capsule repaired through the conventional approach; the tensile stress in the lower part of the conventionally repaired capsule reached the ultimate tensile stress measured on the capsule specimens at a 90° flexion. CONCLUSIONS The finite element model allows dynamic, quantitative and visual assessment of stress distribution in the hip joint capsule, and compared with the conventional approach, anatomical repair can achieve better biomechanical properties of the capsule.
Arthroplasty, Replacement, Hip ; Biomechanical Phenomena ; Finite Element Analysis ; Hip Joint/surgery* ; Humans ; Prognosis ; Stress, Mechanical

Objective To investigate the influence of carotid artery stenting (CS)of asymptomatic critical internal carotid artery (ICA)stenosis patients on cognitive function .Methods One hundred and fifty‐six asymptomatic patients with internal carotid arter‐y stenosis(carotid stenosis severity≥70% )were enrolled ,in whom CS was attempted .Functional assessments including alzheimer disease assessment scale‐cognitive subtest (ADAS‐Cog) ,mini‐mental state examination (MMSE) ,and trail making test A(TMTa) and B(TMTb) were done prior to 1 weeks and 3 months after the procedure .Results Successful CS was achieved in all of patients (100% ) ,only 1 patient was lost to follow‐up .There were significant improvement in ADAS‐Cog score(pre 6 .60 ± 2 .04 vs .post 5 .16 ± 1 .63 ,P<0 .01) ,MMSE score (pre 26 .32 ± 1 .06 vs .post 27 .05 ± 1 .46 ,P< 0 .01) ,TMTa (pre 108 .94 ± 17 .42 vs .post 94 .70 ± 20 .27 ,P<0 .01) ,TMTb (pre 178 .65 ± 21 .77 vs .post 148 .92 ± 23 .65 ,P<0 .01) .There was new cerebral infarction dur‐ing 3 months after surgery .Conclusion Asymptomatic critical internal carotid artery (ICA)stenosis may be one reason of cognitive impairment ,and successful CS could improve cognitive function in asymptomatic ICA stenosis .

Our primary health care institution began to implement national essential medicine system in 2009. In past fi ve years, the goal of national essential medicine system has been initially achieved. For examples, medicine price is steadily reducing, the quality of medical services is improving and residents' satisfaction is substantial increasing every year. However, at the same time, we also found some urgent problems needed to be solved. For examples, the range of national essential medicine is limited, which is difficult to guarantee the quality of essential medication. In addition, how to compensate the primary health care institution is still a question.
China ; Health Services Needs and Demand ; Primary Health Care ; organization & administration

BACKGROUND:Differences of knee anthropometry between individuals are significant, while preoperative templating is not accurate in predicting the prosthesis size.
OBJECTIVE:To improve the accuracy of pre-operative plan in predicting the prosthesis size in total knee arthroplasty using digital technologies.
METHODBetween January 2013 and May 2004, 50 patients (20 men and 30 women;aged 54-82 years;mean age, 67.8 years) received primary total knee arthroplasty for osteoarthritis and were retrospectively analyzed. According to the treatment, the patients were divided into two groups. The digital group, a series of 21 patients, underwent 64-row MDCT before total knee replacement. CT images were imported into Mimics, and three-dimensional models of femur and tibia were reconstructed. Then, computer-aided design files of different sizes of prostheses provided by the manufacturers were imported into Mimics, too. Surgical simulation of osteotomy and prostheses implantation were performed in Mimics, component size was determined by the contour of distal femur and proximal tibia. The control group, a series of 29 patients, underwent primary total knee arthroplasty using conventional approaches. The agreement between preoperative plan and the actual prosthesis size was assessed during the surgery. Postoperative X-ray of low limb was taken to evaluate the accuracy of sizing and the efficacy of digital technologies was assessed.
RESULTS AND CONCLUSION:The intraoperative and postoperative evaluation showed inaccurate sizing of femoral and tibial components in 1 case in digital group and in 11 cases in conventional group. The accuracy of prediction was 95%in digital group and 62%in conventional group, with significant differences between the two groups (P<0.05). Four overhanging and two notching cases were observed in conventional group, but none in digital group. The digital technologies provide an effective means for accurate prediction of prosthesis size and personalized surgical simulation.

Objective To promote the standardization of medical practice in China by comparing the discrepancies of diagnosis and medication strategies for benign prostatic hyperplasia (BPH) between urologists and geriatricians.Methods Departments of urology and geriatrics in general hospitals in China were selected through stratified sampling and 145 315 patients who went for the outpatient service in certain days during December 2011 to December 2012 were recruited by cluster.Questionnaires were completed by corresponding doctors and data of patient clinical characteristics as well as diagnostic and therapeutic pattern were collected.Results A total of 142 511 valid questionnaires were collected with 119 426 from urology and 23 085 from geriatrics.The average age of BPH patients was (68.34±8.61) years and the average IPSS was 17.93±4.73.The rates of diagnostic method were IPSS (99.2％),ultrasonic inspection (86.0％),digital rectal examination (DRE) (66.0％) and urine flow rate test (55.2％).The rate of ultrasonic application was lower while the rates of other methods were higher among urologists (P＜0.01) ; the rate of DRE among urologists was 2.2 times to that among geriatricians.For patients with moderate or severe symptoms,most urologists (72.1％ in moderate patients and 79.9％ in severe patients) applied drug-combination strategy and the rate was 2 times to that among geriatricians (P＜0.01).In contrast,most geriatricians (59.7％ in moderate patients and 56.1％ in severe patients) applied single drug to BPH patients.Urologists utilized α-receptor blockers,plant preparations and traditional Chinese medicine more frequently than geriatricians (P＜0.01).Conclusions Urologists performed more integrated diagnosis strategy compared with geriatricians.The urologists tended to use 5α-reductase inhibitor combined with α-receptor blocker to treat BPH patients with moderate or severe symptoms,while geriatricians preferred 5α-reductase inhibitor alone.

BACKGROUND:Recently, the number of elder patients with femoral neck fracture increased. It is controversial if patients aged over 75 years should receive total hip replacement or hemiarthroplasty. To select a reasonable surgical manner is of great significance for increasing surgical safety, improving hip joint function, elevating quality of life, decreasing postoperative complications, and reducing revision rate.
OBJECTIVE:To retrospectively analyze data of patients aged over 75 years after hip replacement, to compare the advantages and disadvantages, and to find a precise indication.
METHODS:Case data of 171 patients undergoing total hip replacement (observation group) (n=51) or hemiarthroplasty (control group) (n=120) were included. Their differences were compared using basic diseases, operation time, bleeding amount, postoperative complications, postoperative hospitalization day, Harris score at 1 week and 3 months after operation.
RESULTS AND CONCLUSION:Patients in both groups were fol owed up for 3 to 39 months (averagely 23 months). No significant difference in basic diseases, average age, postoperative complications, postoperative hospitalization day, and Harris score at 1 week was detected between the two groups (P>0.05). Harris score and excellent and good rate at 3 months were better in the total hip replacement group than that in the hemiarthroplasty group (P<0.05). Results indicated that strict choice of indication achieved good short-period efficiency in two groups. Thus, hip function of elder patients was early recovered. Quality of life was obviously elevated. The recovery of hip function was relatively better at 3 months in observation group. The incidence of postoperative complications did not increase obviously. These results suggested that besides sufficient preparation, total hip replacement should be the first choice for elder patients.