BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Objective To investigate the anatomical characteristics of the right top pulmonary vein(RTPV),a rare variant pulmonary vein displayed on chest CT,and its clinical significance in thoracoscopic right lung surgery.Methods The clinical data from 27 patients who underwent thoracoscopic right lung surgery were collected.Of these,24 patients were diagnosed with RTPV by preoperative chest CT.The anatomical characteristics were analyzed in combination with three-dimensional reconstruction.Three cases were diagnosed with RTPV based on preoperative chest CT after abnormal veins behind the intermediate bronchus were identified during surgery.Results Of the 27 patients of RTPV,22 cases drained blood from the posterior segment of the right upper lobe(S2),4 cases drained blood from both the S2 and S6a,and 1 case drained blood from both the S2 and S1a.After crossing behind the intermediate bronchus,13 cases returned blood to the lower pulmonary vein,5 cases returned blood to V6,7 cases returned blood to the left atrium,and 2 cases returned blood to the root of the upper pulmonary vein.The vascular diameter of the RTPV was(5.1±1.7)mm.All 27 patients successfully completed thoracoscopic surgery without massive hemorrhage caused by accidental injury to the PTRV.The intraoperative anatomy corresponded to the preoperative chest CT and three-dimensional reconstruction.The intraoperative bleeding volume was(44.6±43.7)mL,and there was no massive hemorrhage caused by accidental injury to the RTPV.Nine patients underwent right lower lobectomy,and four patients had the RTPV preserved,with no postoperative hemoptysis.Five patients underwent RTPV transection,of which two experienced transient hemoptysis following surgery with no serious complications.Conclusion Chest thin-section CT can be applied to diagnose RTPV.Preoperative identification via CT is crucial to avoid massive hemorrhage resulting from accidental injury during thoracoscopic surgery of the right lung.RTPV can be preserved as appropriate in patients undergoing right lower lobectomy.

Objective To investigate the anatomical characteristics of the right top pulmonary vein(RTPV),a rare variant pulmonary vein displayed on chest CT,and its clinical significance in thoracoscopic right lung surgery.Methods The clinical data from 27 patients who underwent thoracoscopic right lung surgery were collected.Of these,24 patients were diagnosed with RTPV by preoperative chest CT.The anatomical characteristics were analyzed in combination with three-dimensional reconstruction.Three cases were diagnosed with RTPV based on preoperative chest CT after abnormal veins behind the intermediate bronchus were identified during surgery.Results Of the 27 patients of RTPV,22 cases drained blood from the posterior segment of the right upper lobe(S2),4 cases drained blood from both the S2 and S6a,and 1 case drained blood from both the S2 and S1a.After crossing behind the intermediate bronchus,13 cases returned blood to the lower pulmonary vein,5 cases returned blood to V6,7 cases returned blood to the left atrium,and 2 cases returned blood to the root of the upper pulmonary vein.The vascular diameter of the RTPV was(5.1±1.7)mm.All 27 patients successfully completed thoracoscopic surgery without massive hemorrhage caused by accidental injury to the PTRV.The intraoperative anatomy corresponded to the preoperative chest CT and three-dimensional reconstruction.The intraoperative bleeding volume was(44.6±43.7)mL,and there was no massive hemorrhage caused by accidental injury to the RTPV.Nine patients underwent right lower lobectomy,and four patients had the RTPV preserved,with no postoperative hemoptysis.Five patients underwent RTPV transection,of which two experienced transient hemoptysis following surgery with no serious complications.Conclusion Chest thin-section CT can be applied to diagnose RTPV.Preoperative identification via CT is crucial to avoid massive hemorrhage resulting from accidental injury during thoracoscopic surgery of the right lung.RTPV can be preserved as appropriate in patients undergoing right lower lobectomy.

Objective:To analyze the clinical efficacy of three-dimensional(3D) reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy for the pulmonary nodules.Methods:We retrospectively analyzed 50 patients with nodules who underwent uniportal fluorescence thoracoscopic subsegmentectomy from December 2021 to February 2024. All patients underwent thin-slice CT scanning and 3D reconstruction preoperatively. 12 patients were given CT-guided hookwire localization preoperatively.The intersegmental plane was identified by fluorescence method.Results:One patient was converted to right upper lobectomy due to no lesion found in S1b. The mean blood loss was(23.4±16.5)ml and the mean operative time was(126.5±38.5)min. The mean duration of postoperative drainage was(2.6±0.8)days. Mean postoperative hospitalization was(4.8±1.8)days. There were 2 cases with postoperative pulmonary infections, including one with encapsulated pleural effusion. There was no air leakage over 3 days, and no death within 30 days after surgery.Conclusion:3D reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy is a safe and feasible technique for resection of pulmonary nodules in lung subsegments, and surgical indications must be strictly controlled.

Objective To compare the clinical application of empirical thoracoscopic segmentectomy and precise segmentectomy planned by artificial intelligence software, and to provide some reference for clinical segmentectomy. Methods A retrospective analysis was performed on the patients who underwent thoracoscopic segmentectomy in our department from 2019 to 2022. The patients receiving empirical thoracoscopic segmentectomy from January 2019 to September 2021 were selected as a group A, and the patients receiving precise segmentectomy from October 2021 to December 2022 were selected as a group B. The number of preoperative Hookwire positioning needle, proportion of patients meeting oncology criteria, surgical time, intraoperative blood loss, postoperative chest drainage time, postoperative hospital stay, and number of patients converted to thoracotomy between the two groups were compared. Results A total of 322 patients were collected. There were 158 patients in the group A, including 56 males and 102 females with a mean age of 56.86±8.82 years, and 164 patients in the group B, including 55 males and 109 females with a mean age of 56.69±9.05 years. All patients successfully underwent thoracoscopic segmentectomy, and patients whose resection margin did not meet the oncology criteria were further treated with extended resection or even lobectomy. There was no perioperative death. The number of positioning needles used for segmentectomy in the group A was more than that in the group B [47 (29.7%) vs. 9 (5.5%), P<0.001]. There was no statistical difference in the number of positioning needles used for wedge resection between the two groups during the same period (P=0.572). In the group A, the nodule could not be found in the resection target segment in 3 patients, and the resection margin was insufficient in 10 patients. While in the group B, the nodule could not be found in 1 patient, and the resection margin was insufficient in 3 patients. There was a statistical difference between the two groups [13 (8.2%) vs. 4 (2.4%), P=0.020]. There was no statistical difference between the two groups in terms of surgical time, intraoperative blood loss, duration of postoperative thoracic drainage, postoperative hospital stay, or conversion to open chest surgery (P＞0.05). Conclusion Preoperative surgical planning performed with the help of artificial intelligence software can effectively guide the completion of thoracoscopic anatomical segmentectomy. It can effectively ensure the resection margin of pulmonary nodules meeting the oncological requirements and significantly reduce the number of positioning needles of pulmonary nodules.

Objective:To discuss the feasibility of control the pulmonary artery (PA) with rumel and bulldog clamp during uniportal thoracoscopic left upper lobectomy.Methods:Retrospective analysis of clinical data of 21 patients whose left PA infiltrated by tumor or lymph nodes.The Rumel was used to proximal control of the left PA, and the endoscopic bulldog clamp to distal control. The left upper lobectomy and PA reconstruction were completed under single-port thoracoscopy.Results:All patients were successfully operated, one patient underwent thymectomy, and one patient underwent left S6a subsegmentectomy at the same time. PA reconstruction was performed by running suture under single-port thoracoscopy in 18 patients, by pericardial patch in 2 patients assisted by small incision, and by circumferential resection in one patient associated with left upper sleeve lobectomy assisted by small incision. The operation time was (213.3±40.5) min, the PA control time was (16.5±4.6) min.The blood loss was (152.9±99.9) ml. Postoperative indwelling time of thoracic drainage tube was (5.3±2.8) days, and the postoperative hospitalization time was (9.1±3.6) days. There were no serious complications during the perioperative period.Conclusion:The PA control technique using rumel and bulldog clamp is reliable and occupies less space, which is helpful for the left upper lobectomy and PA reconstruction under uniportal thoracoscopy

Objective    To summarize the clinical experience of thoracoscopic combined subsegmentectomy (CSS). Methods    The clinical data of 76 patients who underwent thoracoscopic CSS in Anqing Municipal Hospital from May 2018 to July 2022 were retrospectively analyzed, including 22 males and 54 females, aged 27.0-76.0 (54.3±10.5) years. All patients underwent preoperative three-dimensional computed tomography bronchography and angiography using dual source CT. The modified inflation-deflation technique or indocyanine green was used to identify the intersubsegmental border. Results    A total of 86 pulmonary nodules were resected in 76 patients. One patient of left upper lobe S1+2c+S4a, 1 patient of right upper lobe S2b+S3a and 1 patient of right upper lobe S1b+S3b were further performed lobectomy due to insufficient margin. One patient of left upper lobe S1+2+S3a was further performed left upper division segmentectomy due to residual atelectasis. One patient of left upper lobe S1+2c+S3a was further performed left upper division segmentectomy due to B3b+c injury, and the rest completed planned surgeries successfully. The operative time was 90.0-350.0 (174.9±53.2) min. The operative hemorrhage volume was 50.0 (20.0, 50.0) mL. The postoperative hospital stay time was 6.0 (5.0, 7.0) d. Postoperative complications included pulmonary infection in 9 patients, hemoptysis in 3 patients, persistent pulmonary leakage>3 d in 4 patients, pneumothorax in 1 patient, pleural effusion in 1 patient, and myocardial infarction in 1 patient. All of the patients were cured and discharged without perioperative death. Conclusion    Thoracoscopic CSS is relatively complex. Preoperative planning under three-dimensional reconstruction and intraoperative fine operation are helpful for safe completion.

Objective:To investigate the application of three-dimensional image reconstruction combined with problem-based learning (PBL) in the teaching of physicians receiving continuing education in thoracic surgery.Methods:A total of 68 physicians who received continuing education in Department of Thoracic Surgery in our hospital were selected as research subjects, and they were divided into control group and observation group using a random number table, with 34 physicians in each group. The physicians in the control group received traditional teaching, while those in the observation group received three-dimensional image reconstruction combined with PBL teaching. A questionnaire survey, theoretical assessment, and assessment of practical skills were performed to evaluate the effect of teaching. SPSS 22.0 was used to perform the t-test. Results:Compared with the control group, the observation group had significantly higher degrees of satisfaction with each item of the questionnaire survey ( P<0.05). Compared with the control group, the observation group had significantly higher scores of theoretical assessment [(94.07±6.03) vs. (86.34±5.46), P<0.001] and the assessment of practical skills [(95.20±5.48) vs. (84.71±6.14), P<0.001]. Conclusion:The application of three-dimensional image reconstruction combined with PBL teaching can help to improve the comprehensive ability of physicians receiving continuing education.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.