Influence of hip prosthesis position on postoperative gait in symptomatic hip osteoarthritis secondary to hip dysplasia patients after primary total hip arthroplasty: a short-term follow-up study.

BACKGROUND: The aim of this study was to analyze the influence of the positioning of the components of total hip arthroplasty (THA) evaluated by the acetabular anteversion (AA) and femoral anteversion (FA) angle on postoperative gait in patients with symptomatic hip osteoarthritis secondary to hip dysplasia undergoing THA. METHODS: Between May 2023 and May 2024, patients with symptomatic hip osteoarthritis secondary to hip dysplasia (Crowe Type I and IV) who underwent THA were enrolled in the study. The AA angle and FA angle were measured by computer tomography (CT). Gait data were determined by using the Dynamic Right Gait & Posture analysis system. The relationship between FA, AA and gait data was analyzed by Pearson correlation test, subgroup Pearson correlation test, multiple linear regression. RESULTS: A total of 40 patients (45hips) were included in the study. Compared with preoperative, the patient's postoperative foot progression angle, foot contact angle, plantarflexion velocity, swing foot speed, gait velocity, cadence, stride length were significantly improved. Preoperative FA is significantly different from postoperative FA (P < 0.05), while the difference between preoperative and postoperative AA is not significant. BMI, Crowe Type, AA were related to change of cadence. The less the postoperative AA of patients, and the more the cadence in the postoperative gait of patients. CONCLUSION: Our study showed that THA could improve the gait function of patients with symptomatic hip osteoarthritis secondary to hip dysplasia. Adjusting AA lower could obtain a much more postoperative cadence.

Fabrication of sulfur-based functionalized activated carbon as solid phase extraction adsorbent for selective analysis of selenite in water.

Based on the important feature of sulfur with excellent selectivity toward selenite in the presence of selenate, a simple and low-cost adsorbent of solid phase extraction known as sulfur loading activated carbon (SAC-6) was successfully prepared and applied for selenite (Se(IV)) analysis in water. Microstructure and morphological characteristics of SAC-6 had been identified by XRD, TEM, BET and FT-IR. In the static adsorption experiments, Se(IV) could be separated in a wide range of pH values (pH=3-11). The retention process of Se(IV) onto SAC-6 was characterized as spontaneous exothermic reaction. An obvious change of adsorption mechanism occurred in static and dynamic adsorption processes shown that the behaviors followed monolayer and hybrid adsorption. The theoretical maximum adsorption capacity of SAC-6 calculated by Langmuir-Freundlich was 13.48 mg/g. The microcolumn filled with SAC-6 was applied to extract Se(IV) in water solution. The detection limit of Se(IV) analytical procedure was confirmed as 0.27 µg/L within a linear range of 10-1000 µg/L. A good precision with relative standard deviation of 1.34 % (100 µg/L, n = 6) was achieved. The high adaptability and accuracy of SAC-6 microcolumn was validated by analyzing natural water samples and certified reference materials. Our work successfully excavated the application value of the sulfur selectivity, and also provided a new adsorbent for Se(IV) extraction and analysis.

Identification of prevention marker associated with DNA replication in ovarian cancer: Expression of MCM2 protein and bioinformatics analysis.

Ovarian cancer is one of the types of gynecological cancers that is considered to be particularly dangerous. Ovarian cancer treatment has come a long way in recent years, but the disease is still quite likely to spread to other parts of the body. In this line of research, our goal is to pinpoint the shifts in gene expression profiles that are responsible for the avoidance of ovarian cancer. The dataset GSE54388 which was deposited in the Gene Expression Omnibus (GEO) database was processed in order to find differentially expressed genes (DEGs) that were present between human ovarian surface epithelium samples and tumor epithelial component samples. The weighted gene correlation network analysis, also known as WGCNA, was performed on the modules that were associated with the ovarian cancer group. The Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the Gene Set Enrichment Analysis (GSEA) were used to compile a summary of the DEGs that were found in the Venn analysis of the Royalbule module. This analysis found 186 genes that overlapped in the royal blue module. Using the cytohubba plug-in that is included in the Cytoscape software, the Protein-protein Interaction (PPI) network was created and then searched to identify hub genes. Based on these findings, it seems that 10 genes have a role as hub genes in the prevention of ovarian cancer.

Role of Kir4.1/Kir5.1 in mediating Angiotensin-II (Ang-II)-induced stimulation of thiazide-sensitive Na-Cl cotransporter.

Background: Angiotensin-II (Ang-II) perfusion stimulates Kir4.1/Kir5.1 in the distal-convoluted-tubule (DCT) and thiazide-sensitive Na-Cl-cotransporter (NCC). However, the role of Kir4.1/Kir5.1 in mediating the effect of Ang-II on NCC is not understood. Methods: We used immunoblotting and patch-clamp-experiments to examine whether Ang-II-induced stimulation of NCC is achieved by activation of Kir4.1/Kir5.1 of the DCT using kidney-renal-tubule-specific AT1aR-knockout (Ks-AT1aR-KO), Ks-Kir4.1-knockout and the corresponding wild-type mice. Results: Ang-II perfusion for 1, 3 and 7 days progressively increased phosphor-NCC (pNCC) and total-NCC (tNCC) expression and the effect of Ang-II-perfusion on pNCC and tNCC was abolished in Ks-AT1aR-KO. Ang-II perfusion for 1-day robustly stimulates Kir4.1/Kir5.1 in the late DCT (DCT2) and to a lesser degree in the early DCT (DCT1), an effect was absent in Ks-AT1aR-KO mice. However, Ang-II perfusion for 7-days did not further stimulate Kir4.1/Kir5.1 in the DCT2 and only modestly increased Kir4.1/Kir5.1-mediated K + currents in DCT1. Deletion of Kir4.1 not only significantly decreased the expression of pNCC and tNCC but also abolished the effect of 1-day Ang-II perfusion on the expression of phospho-with-no-lysine-kinase-4 (pWNK4), phosphor-ste-20-proline-alanine-rich-kinase (pSPAK), pNCC and tNCC. However, 7-days Ang-II perfusion was still able to significantly stimulate the expression of pSPAK, pWNK4, pNCC and tNCC, and increased thiazide-induced natriuresis in kidney-tubule-specific Kir4.1 knockout (Ks-Kir4.1 KO) mice without obvious changes in K + channel activity in the DCT. Conclusions: Short-term Ang-II induced stimulation of pWNK4, pSPAK and pNCC depends on Kir4.1/Kir5.1 activity. However, long-term Ang-II is able to directly stimulate pWNK4, pSPAK and pNCC by a Kir4.1/Kir5.1 independent mechanism.

Preoperative albumin-bilirubin score predicts short-term outcomes and long-term prognosis in colorectal cancer patients undergoing radical surgery.

BACKGROUND: The albumin-bilirubin (ALBI) score is a serum biochemical indicator of liver function and has been proven to have prognostic value in a variety of cancers. In colorectal cancer (CRC), a high ALBI score tends to be associated with poorer survival. AIM: To investigate the correlation between the preoperative ALBI score and outcomes in CRC patients who underwent radical surgery. METHODS: Patients who underwent radical CRC surgery between January 2011 and January 2020 at a single clinical center were included. The ALBI score was calculated by the formula (log10 bilirubin × 0.66) + (albumin × -0.085), and the cutoff value for grouping patients was -2.8. The short-term outcomes, overall survival (OS), and disease-free survival (DFS) were calculated. RESULTS: A total of 4025 CRC patients who underwent radical surgery were enrolled in this study, and there were 1908 patients in the low ALBI group and 2117 patients in the high ALBI group. Cox regression analysis revealed that age, tumor size, tumor stage, ALBI score, and overall complications were independent risk factors for OS; age, tumor stage, ALBI score, and overall complications were identified as independent risk factors for DFS. CONCLUSION: A high preoperative ALBI score is correlated with adverse short-term outcomes, and the ALBI score is an independent risk factor for OS and DFS in patients with CRC undergoing radical surgery.

Does one-stitch method of temporary ileostomy affect the stoma-related complications after laparoscopic low anterior resection in rectal cancer patients?

PURPOSE: This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). METHODS: We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle-Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. RESULTS: Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = - 17.73, 95%CI = - 25.65 to - 9.80, P < 0.01) and the stoma reversal surgery (MD = - 18.70, 95%CI = - 22.48 to -14.92, P < 0.01) than patients in the TM group. There was no significant difference in intraoperative blood loss of the primary LLAR surgery (MD = - 2.92, 95%CI = - 7.15 to 1.32, P = 0.18). Moreover, patients in the OM group had fewer stoma-related complications than patients in the TM group (OR = 0.55, 95%CI = 0.38 to 0.79, P < 0.01). CONCLUSION: The OM group had shorter operation time in both the primary LLAR surgery and the stoma reversal surgery than the TM group. Moreover, the OM group had less stoma-related complications.

The "appearing" and "disappearing" ascites in the treatment of colorectal cancer: a case report.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. In the treatment of patients with CRC, oxaliplatin plays a pivotal role, with moderate side effects. Neurotoxicity, myelosuppression, ototoxicity, delayed hypersensitivity reactions, and rhabdomyolysis induced by oxaliplatin have been reported individually. However, the occurrence of oxaliplatin-induced ascites has not been reported previously. The objectives of this case report were to elaborate on the rare occurrence of ascites in a patient with CRC after oxaliplatin therapy and to explore its characteristics and causes. Case description: We report on a case of upper rectal cancer seen in a 65-year-old man who underwent robotic-assisted laparoscopic anterior rectal resection. The patient developed ascites during postoperative adjuvant therapy with oxaliplatin and capecitabine. We ruled out tumor recurrence by laparoscopy, intraoperative biopsy, and biochemistry of the ascites. The patient did not experience a recurrence of ascites after discontinuation of chemotherapy. Conclusion: This case suggests that chemotherapy with oxaliplatin might cause ascites. The mechanism of the oxaliplatin-induced liver injury was further discussed, which might have been the cause of ascite formation. When patients with CRC who underwent chemotherapy with oxaliplatin develop ascites, surgeons should actively determine whether this is a side effect of chemotherapy or is due to tumor recurrence in order to avoid unnecessary surgery.

Clinical Significance of Long Non-Coding RNA SNHG5 in the Diagnosis and Prognosis of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is preventable and requires early screening. The study aimed to examine the clinical values of long non-coding RNA (lncRNA) SNHG5 in COPD diagnosis and prognosis. Out of 160 COPD patients, 80 were in the stable stage and 80 were in the acute exacerbation of COPD stage (AECOPD). SNHG5 expression was detected via qRT-PCR. The survival analysis was conducted using Cox regression analysis and K-M curve. SNHG5 levels significantly reduced in both stable COPD and AECOPD groups compared with the control group, with AECOPD group recording the lowest values. SNHG5 levels were negatively correlated with GOLD stage. Serum SNHG5 can differentiate stable COPD patients from healthy individuals (AUC = 0.805), and can screen AECOPD from stable ones (AUC = 0.910). SNHG5 negatively influenced the release of inflammatory cytokines. For AECOPD patients, those with severe cough and wheezing dyspnea symptoms exhibited the lowest values of SNUG5. Among the 80 AECOPD patients, 16 cases died in the one-year follow-up, all of whom had low levels of SNHG5. SNHG5 levels independently influenced survival outcomes, patients with low SNHG5 levels had a poor prognosis. Thus, lncRNA SNHG5, which is downregulated in patients with COPD (especially AECOPD), can potentially protect against AECOPD and serve as a novel prognostic biomarker for AECOPD.

Machine learning for accurate detection of small airway dysfunction-related respiratory changes: an observational study.

BACKGROUND: The use of machine learning(ML) methods would improve the diagnosis of small airway dysfunction(SAD) in subjects with chronic respiratory symptoms and preserved pulmonary function(PPF). This paper evaluated the performance of several ML algorithms associated with the impulse oscillometry(IOS) analysis to aid in the diagnostic of respiratory changes in SAD. We also find out the best configuration for this task. METHODS: IOS and spirometry were measured in 280 subjects, including a healthy control group (n = 78), a group with normal spirometry (n = 158) and a group with abnormal spirometry (n = 44). Various supervised machine learning (ML) algorithms and feature selection strategies were examined, such as Support Vector Machines (SVM), Random Forests (RF), Adaptive Boosting (ADABOOST), Navie Bayesian (BAYES), and K-Nearest Neighbors (KNN). RESULTS: The first experiment of this study demonstrated that the best oscillometric parameter (BOP) was R5, with an AUC value of 0.642, when comparing a healthy control group(CG) with patients in the group without lung volume-defined SAD(PPFN). The AUC value of BOP in the control group was 0.769 compared with patients with spirometry defined SAD(PPFA) in the PPF population. In the second experiment, the ML technique was used. In CGvsPPFN, RF and ADABOOST had the best diagnostic results (AUC = 0.914, 0.915), with significantly higher accuracy compared to BOP (p < 0.01). In CGvsPPFA, RF and ADABOOST had the best diagnostic results (AUC = 0.951, 0.971) and significantly higher diagnostic accuracy (p < 0.01). In the third, fourth and fifth experiments, different feature selection techniques allowed us to find the best IOS parameters (R5, (R5-R20)/R5 and Fres). The results demonstrate that the performance of ADABOOST remained essentially unaltered following the application of the feature selector, whereas the diagnostic accuracy of the remaining four classifiers (RF, SVM, BAYES, and KNN) is marginally enhanced. CONCLUSIONS: IOS combined with ML algorithms provide a new method for diagnosing SAD in subjects with chronic respiratory symptoms and PPF. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients.

Role of calcineurin in regulating renal potassium (K+) excretion: Mechanisms of calcineurin inhibitor-induced hyperkalemia.

Calcineurin, protein phosphatase 2B (PP2B) or protein phosphatase 3 (PP3), is a calcium-dependent serine/threonine protein phosphatase. Calcineurin is widely expressed in the kidney and regulates renal Na+ and K+ transport. In the thick ascending limb, calcineurin plays a role in inhibiting NKCC2 function by promoting the dephosphorylation of the cotransporter and an intracellular sorting receptor, called sorting-related-receptor-with-A-type repeats (SORLA), is involved in modulating the effect of calcineurin on NKCC2. Calcineurin also participates in regulating thiazide-sensitive NaCl-cotransporter (NCC) in the distal convoluted tubule. The mechanisms by which calcineurin regulates NCC include directly dephosphorylation of NCC, regulating Kelch-like-3/CUL3 E3 ubiquitin-ligase complex, which is responsible for WNK (with-no-lysin-kinases) ubiquitination, and inhibiting Kir4.1/Kir5.1, which determines NCC expression/activity. Finally, calcineurin is also involved in regulating ROMK (Kir1.1) channels in the cortical collecting duct and Cyp11 2 expression in adrenal zona glomerulosa. In summary, calcineurin is involved in the regulation of NKCC2, NCC, and inwardly rectifying K+ channels in the kidney, and it also plays a role in modulating aldosterone synthesis in adrenal gland, which regulates epithelial-Na+-channel expression/activity. Thus, application of calcineurin inhibitors (CNIs) is expected to abrupt calcineurin-mediated regulation of transepithelial Na+ and K+ transport in the kidney. Consequently, CNIs cause hypertension, compromise renal K+ excretion, and induce hyperkalemia.

Prebiotic saccharides polymerization improves the encapsulation efficiency, stability, bioaccessibility and gut microbiota modulation of urolithin A liposomes.

This work was to investigate the effect of four prebiotic saccharides gum arabic (GA), fructooligosaccharide (FOS), konjac glucomannan (KGM), and inulin (INU) incorporation on the encapsulation efficiency (EE), physicochemical stability, and in vitro digestion of urolithin A-loaded liposomes (UroA-LPs). The regulation of liposomes on gut microbiota was also investigated by in vitro colonic fermentation. Results indicated that liposomes coated with GA showed the best EE, bioaccessibility, storage and thermal stability, the bioaccessibility was 1.67 times of that of UroA-LPs. The UroA-LPs coated with FOS showed the best freeze-thaw stability and transformation. Meanwhile, saccharides addition remarkably improved the relative abundance of Bacteroidota, reduced the abundances of Proteobacteria and Actinobacteria. The UroA-LPs coated with FOS, INU, and GA exhibited the highest beneficial bacteria abundance of Parabacteroides, Monoglobus, and Phascolarctobacterium, respectively. FOS could also decrease the abundance of harmful bacteria Collinsella and Enterococcus, and increase the levels of acetic acid, butyric acid and iso-butyric acid. Consequently, prebiotic saccharides can improve the EE, physicochemical stability, gut microbiota regulation of UroA-LPs, and promote the bioaccessibility of UroA, but the efficiency varied based on saccharides types, which can lay a foundation for the application of UroA in foods industry and for the enhancement of its bio-activities.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

Prognostic prediction model of colorectal cancer based on preoperative serum tumor markers.

BACKGROUND: Preoperative serum tumor markers not only play a role in the auxiliary diagnosis and postoperative monitoring in colorectal cancer (CRC), but also have been found to have potential prognostic value. AIM: To analyze whether preoperative serum tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), affect the prognosis of CRC. METHODS: This was a retrospective study conducted in a single center. Patients with nonmetastatic CRC who underwent initial surgery between January 2011 and January 2020 were enrolled and divided into development site and validation site groups at a ratio of 7:3. The independent prognostic factors were screened by Cox regression analysis, and finally, a prognostic nomogram model was established. The newly developed model was tested by internal validation. RESULTS: Eventually, 3526 postoperative patients with nonmetastatic CRC were included in the study. There were 2473 patients at the development site and 1056 patients at the validation site. Age (P < 0.01, HR = 1.042, 95%CI = 1.033-1.051), tumor node metastasis (TNM) classification (P < 0.01, HR = 1.938, 95%CI = 1.665-2.255), preoperative CEA (P = 0.001, HR = 1.393, 95%CI = 1.137-1.707) and CA19-9 (P < 0.01, HR = 1.948, 95%CI = 1.614-2.438) levels were considered independent prognostic factors for patients with nonmetastatic CRC and were used as variables in the nomogram model. The areas under the curve of the development and validation sites were 0.655 and 0.658, respectively. The calibration plot also showed the significant performance of the newly established nomogram. CONCLUSION: We successfully constructed a nomogram model based on age, TNM stage, preoperative CEA, and CA19-9 levels to evaluate the overall survival of patients with nonmetastatic CRC.

Predictors of complications after prophylactic ileostomy reversal for rectal cancer: A retrospective study.

BACKGROUND: Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer (RC), but there were significant differences in the reported risk factors for complications after stoma reversal. No studies have analyzed the risk factors for stoma-related complications and overall postoperative complications separately. AIM: To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with RC. METHODS: This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September 2022. Continuous variables are expressed as the mean ± SD and were analyzed with independent-sample t tests, while frequency variables are expressed as n (%), and the χ2 test or Fisher's exact test was used. Univariate and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related complications. RESULTS: The overall complication rate after ileostomy reversal was 11.4%. Patients with lower preoperative albumin concentration (P < 0.01), greater blood loss (P = 0.017), and longer operative times (P < 0.01) were more likely to experience postoperative complications. The incidence of stoma-related complications was 6.4%. Analysis of the study showed that a higher body mass index (BMI) (P < 0.01), preoperative comorbid hypertension (P = 0.049), time from primary surgery to ileostomy reversal (P < 0.01) and longer operation time (P = 0.010) were more likely to result in stoma-related complications postoperatively. Multivariate logistic regression analysis revealed that a lower preoperative albumin level (P < 0.01, OR = 0.888, 95%CI: 0.828-0.958) was an independent risk factor for overall complications. Moreover, multivariate analysis revealed that BMI (P < 0.01, OR = 1.176, 95%CI: 1.041-1.330) and time from primary surgery to ileostomy reversal (P < 0.01, OR = 1.140, 95%CI: 1.038-1.252) were independent risk factors for stoma-related complications after stoma reversal. CONCLUSION: The preoperative albumin level was a predictor of overall complications. Preoperative BMI and the time from primary surgery to ileostomy reversal were predictors of stoma-related complications.

Neural critic learning with accelerated value iteration for nonlinear model predictive control.

In practical industrial processes, the receding optimization solution of nonlinear model predictive control (NMPC) is always a very knotty problem. Based on adaptive dynamic programming, the accelerated value iteration predictive control (AVI-PC) algorithm is developed in this paper. Integrating iteration learning with the receding horizon mechanism of NMPC, a novel receding optimization solution pattern is exploited to resolve the optimal control law in each prediction horizon. Besides, the basic architecture and the specific form of the AVI-PC algorithm are demonstrated, including the relationship among the iterative learning process, the prediction process, and the control process. On this basis, the convergence and admissibility conditions are established, and the relevant properties are comprehensively analyzed when the accelerated factor satisfies the established conditions. Furthermore, the accelerated value iterative function is approximated through the single critic network constructed by utilizing the multiple linear regression method. Finally, the plentiful simulation experiments are conducted from various perspectives to verify the effectiveness and progressiveness of the AVI-PC algorithm.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Ferroptosis Is Crucial for Cisplatin Induced Sertoli Cell Injury via N6-Methyladenosine Dependent Manner.

PURPOSE: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. MATERIALS AND METHODS: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2',7'-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. RESULTS: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. CONCLUSIONS: Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Automatic measurement of lower limb alignment in portable devices based on deep learning for knee osteoarthritis.

BACKGROUND: For knee osteoarthritis patients, analyzing alignment of lower limbs is essential for therapy, which is currently measured from standing long-leg radiographs of anteroposterior X-ray (LLR) manually. To address the time wasting, poor reproducibility and inconvenience of use caused by existing methods, we present an automated measurement model in portable devices for assessing knee alignment from LLRs. METHOD: We created a model and trained it with 837 conforming LLRs, and tested it using 204 LLRs without duplicates in a portable device. Both manual and model measurements were conducted independently, then we recorded knee alignment parameters such as Hip knee ankle angle (HKA), Joint line convergence angle (JCLA), Anatomical mechanical angle (AMA), mechanical Lateral distal femoral angle (mLDFA), mechanical Medial proximal tibial angle (mMPTA), and the time required. We evaluated the model's performance compared with manual results in various metrics. RESULT: In both the validation and test sets, the average mean radial errors were 2.778 and 2.447 (P<0.05). The test results for native knee joints showed that 92.22%, 79.38%, 87.94%, 79.82%, and 80.16% of the joints reached angle deviation<1° for HKA, JCLA, AMA, mLDFA, and mMPTA. Additionally, for joints with prostheses, 90.14%, 93.66%, 86.62%, 83.80%, and 85.92% of the joints reached that. The Chi-square test did not reveal any significant differences between the manual and model measurements in subgroups (P>0.05). Furthermore, the Bland-Altman 95% limits of agreement were less than ± 2° for HKA, JCLA, AMA, and mLDFA, and slightly more than ± 2 degrees for mMPTA. CONCLUSION: The automatic measurement tool can assess the alignment of lower limbs in portable devices for knee osteoarthritis patients. The results are reliable, reproducible, and time-saving.