BACKGROUND: As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034. METHODS: The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC). RESULTS: Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases that need rehabilitation increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively. CONCLUSIONS The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.
Humans ; China/epidemiology* ; Global Burden of Disease ; Female ; Male ; Musculoskeletal Diseases/epidemiology* ; Rehabilitation/trends* ; Quality of Life ; Middle Aged ; Aged ; Bayes Theorem

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

OBJECTIVE: To investigate the effects and underlying mechanism of ionizing radiation on the adipogenic of mesenchymal stem cells (MSCs). METHODS: Mouse MSCs were cultured in vitro and treated with 2 Gy and 6 Gy radiation with ⁶⁰Co, and the radiation dose rate was 0.98 Gy/min. Bulk RNA-seq was performed on control and irradiated MSCs. The changes of adipogenic differentiation and oxidative stress pathways of MSC were revealed by bioinformatics analysis. Oil Red O staining was used to detect the adipogenic differentiation ability of MSCs in vitro, and real-time fluorescence quantitative PCR (qPCR) was used to detect the expression differences of key regulatory factors Cebpa, Lpl and Pparg after radiation treatment. At the same time, qPCR and Western blot were used to detect the effect of inhibition of Nrf2, a key factor of antioxidant stress pathway, on the expression of key regulatory factors of adipogenesis. Moreover, the species conservation of the irradiation response of human bone marrow MSCs and mouse MSC was determined by qPCR. RESULTS: Bulk RNA-seq suggested that ionizing radiation promotes adipogenic differentiation of MSCs and up-regulation of oxidative stress-related genes and pathways. The results of Oil Red O staining and qPCR showed that ionizing radiation promoted the adipogenesis of MSCs, with high expression of Cebpa, Lpl and Pparg, as well as oxidative stress-related gene Nrf2. Nrf2 pathway inhibitors could further enhance the adipogenesis of MSCs in bone marrow after radiation. Notably, the similar regulation of oxidative pathways and enhanced adipogenesis post irradiation were observed in human bone marrow MSCs. In addition, irradiation exposure led to up-regulated mRNA expression of interleukin-6 and down-regulated mRNA expression of colony stimulating factor 2 in human bone marrow MSCs. CONCLUSION Ionizing radiation promotes adipogenesis of MSCs in mice, and oxidative stress pathway participates in this effect, blocking Nrf2 further promotes the adipogenesis of MSCs. Additionally, irradiation activates oxidative pathways and promotes adipogenic differentiation of human bone marrow MSCs.
Mesenchymal Stem Cells/cytology* ; Oxidative Stress/radiation effects* ; Animals ; Adipogenesis/radiation effects* ; Mice ; Radiation, Ionizing ; Cell Differentiation/radiation effects* ; Humans ; NF-E2-Related Factor 2/metabolism* ; PPAR gamma ; Cells, Cultured

OBJECTIVE: To establish an in vitro cell model simulating acute graft-versus-host disease (aGVHD) bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells (MSCs). METHODS: The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model (n=20) was established by being injected with bone marrow cells (1×10⁷ per mouse) from donor mice within 4-6 hours after receiving a lethal dose (8.0 Gy, 72.76 cGy/min) of γ ray general irradiation. A mouse model of aGVHD (n=20) was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells (1×10⁷ per mouse) and spleen lymphocytes (2×10⁶ per mouse). The blood was removed from the eyeballs and the mouse serum was aspirated on the 7^th day after modeling. Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2%, 5% and 10% BMT mouse serum and aGVHD mouse serum in the medium, respectively. The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining. The expression levels of related proteins PPARγ and CEBPα were detected by Western blot. The expression differences of key adipogenic transcription factors including PPARγ, CEBPα, FABP4 and LPL were determined by real-time quantitative PCR (RT-qPCR). RESULTS: An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established. Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10% compared with BMT serum. Western blot experiments showed that adipogenesis-related proteins PPARγ and CEBPα expressed in MSCs were down-regulated. Further RT-qPCR assay showed that the production of PPARγ, CEBPα, FABP4 and LPL, the key transcription factors for adipogenic differentiation of MSC, were significantly reduced. CONCLUSION The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.
Animals ; Mesenchymal Stem Cells/cytology* ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Adipogenesis ; Female ; Cell Differentiation ; Graft vs Host Disease/blood* ; Bone Marrow Cells/cytology* ; PPAR gamma/metabolism* ; Disease Models, Animal ; CCAAT-Enhancer-Binding Protein-alpha/metabolism*

OBJECTIVE: To prepare clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with high expression of hematopoietic supporting factors and evaluate their stem cell characteristics. METHODS: Fetal umbilical cord tissues were collected from healthy postpartum women during full-term cesarean section. Wharton's jelly was mechanically separated and hUC-MSCs were obtained by explant culture method and enzyme digestion method in an animal serum-free culture system with addition of human platelet lysate. The phenotypic characteristics of hUC-MSCs obtained by two methods were detected by flow cytometry. The differences in proliferation ability between the two groups of hUC-MSCs were identified through CCK-8 assay and colony forming unit-fibroblast (CFU-F) assay. The differences in multilineage differentiation potential between the two groups of hUC-MSCs were identified through induction of adipogenic, osteogenic, and chondrogenic differentiation. The mRNA expression levels of hematopoietic supporting factors such as SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in the two groups of hUC-MSCs were identified by real-time fluorescence quantiative PCR(RT-qPCR). RESULTS: The results of flow cytometry showed that hUC-MSCs obtained by the two methods both expressed high levels of CD73, CD90 and CD105, while lowly expressed CD31, CD45 and HLA-DR. The results of CCK-8 and CFU-F assay showed that the proliferation ability of hUC-MSCs obtained by explant culture method was better than those obtained by enzyme digestion method. The results of the triple lineage differentiation experiment showed that there was no significant difference in multilineage differentiation potential between the two grous of hUC-MSCs. The results of RT-qPCR showed that the mRNA expression levels of hematopoietic supporting factors SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in hUC-MSCs obtained by explant cultrue method were higher than those obtained by enzyme digestion method. CONCLUSION Clinical-grade hUC-MSCs with high expression levels of hematopoietic supporting factors were successfully cultured in an animal serum-free culture system.
Humans ; Mesenchymal Stem Cells/metabolism* ; Umbilical Cord/cytology* ; Cell Differentiation ; Female ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Angiopoietin-1/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Stem Cell Factor/metabolism* ; Flow Cytometry ; Pregnancy

OBJECTIVE: This study aims to analyze the influence factors of lower urinary tract symptoms (LUTS) in patients receiving radical prostatectomy for prostate cancer, and to explore effective nursing strategy in order to provide a theoretical basis for improving the postoperative quality of life of patients. METHODS: A retrospective study was conducted on 103 elderly male patients who underwent radical prostatectomy for prostate cancer in the Department of Urology at General Hospital of Eastern Theater Command from August 2022 to August 2024. The patients were categorized into two groups based on whether LUTS occurred. Demographic and clinical characteristics, perioperative parameters, follow-up data, and participation in pelvic floor muscle training were analyzed to identify risk factors associated with postoperative LUTS. RESULTS: The incidence of postoperative LUTS in the patients with LUTS before the operation was significantly higher than that in the patients without LUTS before the operation (68.42% vs 32.61%, P=0.001). Additionally, the use of larger catheters (22F) was closely associated with an increased incidence of postoperative LUTS(P<0.01). Pelvic floor exercises demonstrated a significant protective effect, with patients who engaged in pelvic floor exercises exhibiting a lower incidence of postoperative LUTS (38.60% vs 60.87%, P=0.040). Regression analysis further revealed that pelvic floor exercises was the protective factor for postoperative LUTS (OR=0.215, 95%CI: 0.091－0.508, P<0.01). CONCLUSION Preoperative LUTS and catheter size are significant risk factors for the occurrence of postoperative LUTS following radical prostatectomy. Pelvic floor muscle exercise after surgery has a protective effect. Postoperative personalized nursing interventions are necessary for different patients to achieve optimal recovery outcomes.
Humans ; Male ; Prostatectomy/adverse effects* ; Retrospective Studies ; Lower Urinary Tract Symptoms/nursing* ; Aged ; Risk Factors ; Quality of Life ; Pelvic Floor ; Prostatic Neoplasms/surgery* ; Postoperative Complications/prevention & control* ; Exercise Therapy ; Middle Aged

OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: To investigate the relationship between the trajectories of serum potassium changes after intensive care unit (ICU) admission and 30-day death risk in patients with sepsis. METHODS: A retrospective cohort study was conducted, including adult patients with sepsis admitted to the comprehensive ICU, medical intensive care unit (MICU) and emergency intensive care unit (EICU) of Guizhou Medical University Affiliated Hospital from January 2020 to January 2024. The patients who had a minimum of 5 days' hospitalisation in the ICU and who had at least 7 consecutive days of the serum potassium measurements were classified into five trajectories groups according to group-based trajectory modelling (GBTM) using SAS software. This was based on tendency changes in serum potassium levels in patients after admission to the ICU, which was categorized as follows: slowly increased from a low level group, slowly increased from a medium level of normal range group, slowly decreased from a medium level of normal range group, slowly decreased from a high level group, and slowly increased from a high level of normal range group. The patient's gender, age, medical history, and white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), activated partial thromboplastin time (APTT), prothrombin time (PT), blood sodium, and serum creatinine (SCr) at the time of admission to the ICU were collected. At the same time, the patient's worst sequential organ failure assessment (SOFA) score within 24 hours of admission to the ICU, length of ICU stay, and 30-day outcome were record. The differences in clinical data among different groups of patients were compared. The 30-day cumulative survival rates of the various serum potassium trajectories were plotted using Kaplan-Meier survival curves, the groups were then compared using the Log-Rank test. A multivariate Cox proportional risk regression analysis was developed to evaluate the independent effect of serum potassium trajectory on 30-day death risk. RESULTS: Finally, 342 ICU sepsis patients were enrolled, of which 42 patients in the slowly increased from a low level group (12.28%), 127 patients in the slowly increased from a medium level of normal range group (37.14%), 118 patients in the slowly decreased from a medium level of normal range group (34.50%), 28 patients in the slowly decreased from a high level group (8.19%), and 27 patients in the slowly increased from a high level of normal range group (7.89%). Except for age and APTT differences, there were no statistically significant differences in other clinical characteristics among the patients in the different serum potassium trajectories groups. Kaplan-Meier survival curves showed that there was statistically significant difference in the 30-day cumulative survival rate among the patients in the different serum potassium trajectories groups (Log-Rank test: χ² = 14.696, P = 0.005), with the lowest in the slowly increased from a high level of normal range group (39.3%). Multivariate Cox proportional risk regression analysis showed that the patients with the serum potassium trajectory of slowly increased from a high level of normal range had the highest 30-day death risk [hazard ratio (HR) = 2.341, 95% confidence interval (95%CI) was 1.049-5.226, P = 0.038]. This association persisted after adjustment for variables such as gender, age, medical history, SOFA score, WBC, PLT, PCT, APTT, PT, blood sodium, and SCr (HR = 3.058, 95%CI was 1.249-7.488, P = 0.014). CONCLUSION Compared with the patients whose serum potassium fluctuated within the normal range, the sepsis patients in the ICU with a serum potassium trajectory that slowly increased from a high level of normal range had a significantly higher 30-day death risk.
Humans ; Retrospective Studies ; Intensive Care Units ; Sepsis/blood* ; Potassium/blood* ; Male ; Female ; Middle Aged ; Aged ; Risk Factors ; Hospital Mortality ; Prognosis