BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

AIM:The aim of our study is to investigate the metabolic profile differences during cervical lesion progression and evaluate their potential clinical value in assisting the diagnosis of cervical cancer(CC).METHODS:Ul-tra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)was em-ployed to conduct non-targeted metabolomic analysis of cervical swab samples from 43 CC patients,34 high-grade squa-mous intraepithelial lesion(HSIL)patients,and 43 healthy controls.Based on the distinct features among the three groups,principal component analysis(PCA)was used to identify the metabolic differences among CC,HSIL and healthy groups.MetaboAnalyst 5.0 was then employed to perform KEGG pathway enrichment analysis on the differential metabo-lites.Finally,random forest machine learning algorithm was used to construct classification prediction models for distin-guishing CC from healthy,HSIL from healthy,and CC from HSIL.The performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 1 543 metabolites were identified across the healthy,HSIL and CC groups after filtration,with 407 metabolites differing between the groups.The study found that metabolite PGE2 was present in all three groups,with its expression levels progressively increasing with the progression of cervical lesions.Differential metabolite enrichment analysis demonstrated that CC is associated with specific cancer-relat-ed metabolic pathways,including the tricarboxylic acid cycle,tyrosine metabolism,tryptophan metabolism,and the pen-tose phosphate pathways.Additionally,the study developed three prediction models based on metabolic products for diag-nosing HSIL and CC:the full model,the simplified model,and the PGE2 model.The results indicated that metabolites ex-hibited strong diagnostic efficiency.Both the full model and the simplified model effectively distinguished CC from HSIL,CC from healthy,and HSIL from healthy.The AUC values for the full model were 0.90,0.92 and 0.84,respectively,while those for the simplified model were 0.81,0.95 and 0.85,respectively.Furthermore,the PEG2 model achieved AUC values of 0.74 and 0.80 for distinguishing CC from healthy and HSIL from healthy,respectively.CONCLUSION:The metabolic profiles of cervical cancer exhibit significant differences during the progression of cervical cancer,and these metabolites hold potential clinical value as biomarkers for cervical lesions.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM:The aim of our study is to investigate the metabolic profile differences during cervical lesion progression and evaluate their potential clinical value in assisting the diagnosis of cervical cancer(CC).METHODS:Ul-tra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)was em-ployed to conduct non-targeted metabolomic analysis of cervical swab samples from 43 CC patients,34 high-grade squa-mous intraepithelial lesion(HSIL)patients,and 43 healthy controls.Based on the distinct features among the three groups,principal component analysis(PCA)was used to identify the metabolic differences among CC,HSIL and healthy groups.MetaboAnalyst 5.0 was then employed to perform KEGG pathway enrichment analysis on the differential metabo-lites.Finally,random forest machine learning algorithm was used to construct classification prediction models for distin-guishing CC from healthy,HSIL from healthy,and CC from HSIL.The performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 1 543 metabolites were identified across the healthy,HSIL and CC groups after filtration,with 407 metabolites differing between the groups.The study found that metabolite PGE2 was present in all three groups,with its expression levels progressively increasing with the progression of cervical lesions.Differential metabolite enrichment analysis demonstrated that CC is associated with specific cancer-relat-ed metabolic pathways,including the tricarboxylic acid cycle,tyrosine metabolism,tryptophan metabolism,and the pen-tose phosphate pathways.Additionally,the study developed three prediction models based on metabolic products for diag-nosing HSIL and CC:the full model,the simplified model,and the PGE2 model.The results indicated that metabolites ex-hibited strong diagnostic efficiency.Both the full model and the simplified model effectively distinguished CC from HSIL,CC from healthy,and HSIL from healthy.The AUC values for the full model were 0.90,0.92 and 0.84,respectively,while those for the simplified model were 0.81,0.95 and 0.85,respectively.Furthermore,the PEG2 model achieved AUC values of 0.74 and 0.80 for distinguishing CC from healthy and HSIL from healthy,respectively.CONCLUSION:The metabolic profiles of cervical cancer exhibit significant differences during the progression of cervical cancer,and these metabolites hold potential clinical value as biomarkers for cervical lesions.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective:To explore the prenatal ultrasound phenotype and genetic basis of two fetuses with Wolf-Hirschhorn syndrome (WHS).Methods:A retrospective analysis was conducted on the ultrasound imaging data of two fetuses suspected for WHS at the Prenatal Diagnostic Center of Qingyuan People′s Hospital in July 2017 and August 2019, respectively. Amniotic fluid samples of the two fetuses were subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). This study was approved by Medical Ethics Committee of the Qingyuan People′s Hospital (Ethics No. IRB-2022-064).Results:Prenatal ultrasound examination of the two fetuses had consistently revealed WHS-associated traits including intrauterine growth restriction (IUGR), craniofacial abnormalities and cardiovascular anomalies. Karyotyping analysis suggested that both fetuses had harbored cryptic chromosomal translocations involving partial deletion of 4p. And parental verification revealed that it was de novo for fetus 1 and paternal for fetus 2. CMA has confirmed that fetus 1 had an approximately 8.7 Mb deletion at 4p16.3p16.1 and a 6.8 Mb duplication at 8p23.1p23.1, whilst fetus 2 had a 20.05 Mb deletion at 4p16.3p15.31 and a 7.66 Mb duplication at 9p24.3p24.1. The karyotype of fetus 1 was determined as 46, XN, der(4)t(4; 8)(p16.1; p23.1)dn.arr[hg19]4p16.3p16.1(68345_8721580)×1, 8p23.3p23.1(158048_6933745)×3, and that of fetus 2 was determined as 46, XN, der(4)t(4; 9)(p15.3; p24)dpat.arr[hg19]4p16.3p15.31(68345_20116061)×1, 9p24.3p24.1(208454_7868292)×3. Conclusion:The 4p deletion is probably the main cause for the WHS phenotype in both fetuses. WHS should be suspected when IUGR, renal anomalies, craniofacial and cardiovascular abnormalities are detected upon prenatal ultrasound screening.

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

Objective:To analyze the clinical characteristics and neurophysiological features of patients with neuralgic amyotrophy (NA) and explore their neurological function status.Methods:Clinical data and neurophysiological findings of 90 patients diagnosed with NA at Beijing Tsinghua Changgung Hospital from September 2016 to January 2024 were collected and their clinical phenotypes and neurophysiological characteristics were systematically summarized and analyzed.Results:Among the 90 patients, males accounted for 60.0% (54 cases) and females accounted for 40.0% (36 cases). The duration of the disease was 12 (3, 36) months (ranged from 1 week to 5 years). The onset age of the patients was 58 (30, 70) (21-87) years. Unilateral involvement was noted in 94.4% (85/90) of patients, exhibiting a left-to-right ratio of 1∶1.3, while only 5.6% (5/90) had bilateral involvement. The majority of patients demonstrated a monophasic clinical course with a recurrence rate of just 2.2% (2/90). The primary clinical manifestations included upper limb pain in 70.0% (63/90) of patients, which progressed to muscle weakness and atrophy within 1 day to 1 month, whereas 30.0% (27/90) of patients without significant pain symptoms. Lesions predominantly affected the upper trunk of the brachial plexus, which accounted for 64.4% (58/90) of patients. Distal nerve injuries in the upper limb were observed in 14.4% (13/90) of patients, with 6.7% (6/90) demonstrating isolated anterior interosseous nerve involvement and another 6.7% (6/90) exhibiting isolated posterior interosseous nerve involvement; 1 case had concurrent anterior and posterior interosseous nerve damage. Additionally, 1 case presented with bilateral phrenic nerve involvement, and another patient had isolated posterior tibial nerve injury. Electrophysiological evaluations of patients with NA revealed that axonal damage to motor nerve fibers was a hallmark feature of the condition. Among patients undergoing motor nerve conduction studies, 68.8% (55/80) exhibited decreased compound muscle action potential amplitude, and 31.3% (25/80) had prolonged latency. Sensory nerve conduction was normal in 60.0% (48/80) of patients, while abnormalities included prolonged latency in 15.0% (12/80), reduced amplitude in 12.5% (10/80), slowed conduction velocity in 8.8% (7/80), and absent waveforms in 3.8% (3/80) of patients. The rates of abnormal nerve conduction findings in motor nerves were the highest in the suprascapular nerve (70.6%, 36/51), followed by the axillary nerve (58.3%, 35/60), musculocutaneous nerve (50.7%, 35/69), long thoracic nerve (6/17), and both anterior and posterior interosseous nerves (7.5%, 6/80 each). In sensory nerves, abnormalities were predominantly noted in the lateral antebrachial cutaneous nerve (30.0%, 12/40). Needle electromyography demonstrated neurogenic damage, most frequently affecting the infraspinatus muscle (69.2%, 18/26), biceps brachii (68.1%, 49/72), and deltoid muscle (65.3%, 47/72). The positive rate of magnetic resonance neurography (MRN) for NA was 62.1% (41/66), among which 63.4% (26/41) showed localized swelling of the brachial plexus, 51.2% (21/41) exhibited T 2 hyperintensity, and 4.9% (2/41) demonstrated denervated changes in the muscles. The positive rate of ultrasound for NA was 71.1% (59/83), with 91.5% (54/59) showing nerve swelling and 8.5% (5/59) exhibiting hourglass constriction .Conclusions:NA is a peripheral neuropathy characterized by spontaneous pain, limb weakness, and (or) muscle atrophy primarily. Its clinical phenotype predominantly involves damage to the upper trunk of the brachial plexus, which can also manifest as isolated mononeuropathy. Neurophysiological findings most commonly reveal the neurogenic damage to the muscles innervated by the upper trunk of the brachial plexus, mainly characterized by the axonal damage to the motor nerves, and pure motor nerve damage may also be observed. MRN and neuroultrasound can assist in qualitative diagnosis.