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

Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treatment status of most patients with malignant tumors.In order to regulate and guide the immunotherapy of cancer patients in China,the Chinese Society of Clinical Oncology(CSCO)has updated the Immune Checkpoint Inhibitor Clinical Practice Guidelines every year since 2020,which has been widely praised.The Version 2024 released this year has been significantly updated in terms of content,which can be summarized in five keywords as:"addition","deletion","upgrade","downgrade"and"definiteness",with the characteristic of a large overall update range,the continuous advancement of immunotherapy,continuous enrichment of combination strategies,more first-line treatment options,and excellent performance of several drugs.This article provides a point-to-point interpretation of major updates in the new guideline.

Objective:To investigate the epidemiological characteristics and genotype trends of rotavirus infection among the population with diarrhea in China, from 2009 to 2020 and provide evidence for strategic surveillance and prevention.Methods:Surveillance data on diarrhea syndrome from 252 sentinel hospitals across 28 provinces (municipalities, autonomous regions) were obtained from the information management system of the Infectious Disease Surveillance Technology Platform of the National Science and Technology Major Project. Descriptive epidemiological methods were employed to analyze the distribution of rotavirus diarrhea cases in different climatic zones, populations, and times from 2009 to 2020, as well as the genotyping characteristics and changing trends of group A rotavirus diarrhea cases.Results:From 2009 to 2020, a total of 114 606 diarrhea cases were tested for rotavirus, and the positive rate was 19.1% (21 872/114 606); group A rotavirus was dominant (98.2%, 21 471/21 872). The positive rate of rotavirus was the highest in 2009 (36.9%, 2 436/6 604) and 2010 (30.6%, 5 130/16 790), fluctuated between 14.0% to 18.0% from 2011 to 2017, raised slightly in 2018 (20.3%, 2 211/10 900), and declined continuously in the following two years (15.5%, 2 262/14 611 and 9.5%, 470/4 963). The positive rate of males (20.2%, 13 660/67 471) was significantly higher than that of females (17.4%, 8 212/47 135). Children under five had the highest positive rate (28.4%, 18 261/64 300), more than four times that of adults. The positive rate peaked from December to February in the mediate temperate zone, warm temperate zone, and subtropical zone, while there were two peaks from November to January and May to June in the frigid zone of the plateau. The dominant genotype of group A rotavirus gradually changed from G3P[8] and G1P[8] to G9P[8] during 2009-2020.Conclusions:The overall rotavirus infection rate in China was on a downward trend. Meanwhile, significant variations of positive rates were observed in seasonal epidemics and different age groups from 2009 to 2020. Rotavirus diarrhea in children was still a prominent concern. Vaccination of rotavirus vaccine should be promoted, and the epidemiological characteristics and genotypes of rotavirus diarrhea should be continuously monitored.

Immunotherapy,represented by immune checkpoint inhibitors,may lead to immune-related adverse events(irAEs)while demonstrating favorable efficacy in patients with malignant tumors.Many domestic and international guidelines or consensus have been established to assist clinicians in effectively managing the majority of irAEs.However,further exploration about irAEs is required regarding the definition and determination,temporal patterns,individual variances,utilization of hormones and immunosuppressants,correlation between irAEs and therapeutic outcomes,immune reactivation,and special populations.The identification and management of severe,refractory,and multiple irAEs necessitate additional solutions.This paper aims to clarify 10 prominent issues concerning irAEs individually and provide assistance for clinicians.

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

We retrospectively analyzed the clinical data of seven patients (four men and three women) with primary hyperoxaluria (PH) type 1 (PH1) in the Department of Nephrology of Zhongda Hospital, Southeast University from January 2018 to October 2023. The mean age at disease onset was 32.1 (range: 26-42) years. The mean age at diagnosis was 40.6 (range: 28-51) years. All patients initially had kidney stones, and three patients were found to have renal insufficiency at the time of disease onset. Among them, two patients underwent hemodialysis immediately. Symptoms at the first visit included bone pain ( n=7), joint pain or deformity ( n=5), fatigue ( n=5), hypotension ( n=3), and subcutaneous nodules ( n=2). Four patients had a family history of PH. All patients had varying degrees of anemia (60-114 g/L), significant hypoalbuminemia (16.5-32.1 g/L), and hypercoagulable state (D-dimer: 2 230-12 781 μg/L). Seven patients received maintenance hemodialysis; their mean age was 37.7 (range: 26-50) years. The mean duration from disease onset to hemodialysis was 5.6 (range: 0-20) years. Five patients repeatedly experienced dialysis access dysfunction. Three patients underwent kidney transplantation before a diagnosis was made, and all transplanted kidneys lost function due to oxalate deposition. The mean follow-up duration was 14.43 (range: 4-38) months. Unfortunately, one patient died. All seven patients underwent computed tomography of the abdomen. All patients suffered skeletal abnormalities, bilateral nephrolithiasis, and nephrocalcinosis. Six patients carried AGXT gene mutations, including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included: c.823-824dup.AG (p.S275Rfs*38)(exon 8), c.815-816ins.GA (p.S275Rfs*38)(exon 8), c.595G>A (p.G199S) (exon 5), c.32C>G (p.P11R) (exon 1), and c.638C>T (p.A213V)(exon 6). According to the American College of Medical Genetics and Genomics guidelines, two loci were identified as likely pathogenic variants, seven were identified as pathogenic variants, and one locus was identified as having uncertain significance. In addition, patients 1 and 4 underwent skin biopsy, patient 2 underwent renal transplant biopsy, and patient 3 underwent bone marrow biopsy. Interestingly, significant oxalate deposition was found in the tissues. Therefore, PH1 is a rare autosomal recessive inherited disease. This study not only enhanced the understanding of the clinical characteristics of PH1 patients but also had great significance in early diagnosis and treatment of the disease.

The paper reports a rarely case of hemophagocytic syndrome complicated with thrombotic microangiopathy, first presented with fever of unknown origin. A 37-year-old female patient mainly presented with fever, hemolytic anemia, thrombocytopenia, and progressive decline in renal function. After infusion of fresh frozen plasma and high dose of glucocorticoid after double plasma exchange, the patient showed good prognosis, no further fever or hemolysis occurred, recovered platelet and renal function. After acute episode phase, kidney biopsy was performed and acute tubular necrosis was diagnosed. During the follow-up period, the disease did not recur, and the renal function was normal.

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 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.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a catastrophic impact on human life and economic life. Due to the combination of multiple underlying diseases and low vaccination rates, dialysis patients are susceptible to SARS-CoV-2 infection and are likely to have more severe illness and even death. Moreover, dialysis patients with SARS-CoV-2 infection may initially present as asymptomatic or with mild symptoms, which makes it very difficult to identify severe patients at an early stage. Here, the epidemiology, clinical characteristics, risk factors for prognosis, vaccination and therapeutic strategies of dialysis patients with SARS-CoV-2 infection were summarized and analyzed, and it is hoped to provide a reference for the diagnosis and treatment of SARS-CoV-2 infection in this special group of patients.