Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the clinical and pathological characteristics, treatment and prognosis of endometriosis (EM)-associated ovarian mesonephric-like adenocarcinoma (MLA).Methods:Clinical and pathological data were collected from nine patients diagnosed with EM-associated ovarian MLA at the Obstetrics and Gynecology Hospital of Fudan University between January 2022 and December 2024. Histological slides were re-reviewed, immunohistochemical examination and molecular testing were performed, and patient follow-up was conducted.Results:(1) Clinical characteristics: the median age of the nine patients was 54 years (range: 38-69 years). All patients presented with a pelvic mass; five cases also reported abdominal pain. Tumor location included five cases in the right ovary, two in the left ovary, and two involving both ovaries. International Federation of Gynecology and Obstetrics (FIGO) staging showed 3 cases at stage Ⅰ, 4 at stage Ⅱ, and 2 at stage Ⅲ. (2) Pathological features: gross examination revealed mixed solid-cystic masses with solid areas appearing gray-white or yellow-brown; the median maximum tumor diameter was 9.0 cm (range: 2.6-13.0 cm). Microscopically, tumors exhibited various architectural patterns, including tubular, glandular, papillary, slit-like, sex cord-like, glomeruloid, and solid structures, with tubular and glandular patterns being most common. Tumor cells demonstrated mild to moderate nuclear atypia. Of the 11 tumor foci in the 9 cases, 8 showed coexistence of MLA with other tumor components, such as endometrioid carcinoma, borderline endometrioid or borderline seromucinous tumors. In 1 case of MLA mixed with a borderline endometrioid tumor, both components exhibited squamous metaplasia. Immunohistochemistry showed variable expression of GATA-binding protein 3, thyroid transcription factor-1, CD 10, and calretinin, with positive rates of 9/11, 8/11, 5/11, and 3/6, respectively. Two tumor foci (2/11) exhibited focal expression of estrogen receptor and progesterone receptor. All cases displayed wild-type p53 expression. Molecular testing via next-generation sequencing in five patients revealed pathogenic mutations in the KRAS gene (5/5), with 3 cases (3/5) harboring additional pathogenic mutations in other genes. (3) Treatment and prognosis: all patients underwent surgery, supplemented by chemotherapy and (or) targeted therapy. Five patients underwent comprehensive staging surgery, four received cytoreductive surgery, and one patient received targeted therapy. The median follow-up duration was 7 months (range: 2-27 months). Three patients (3/9) experienced recurrence, and no deaths were reported during the follow-up period. Conclusions:EM-associated ovarian MLA demonstrates diverse morphological patterns and frequently coexists with other tumor types. Accurate diagnosis relies on an integrated evaluation of histomorphology, immunohistochemistry, and molecular testing. The primary treatment for EM-associated ovarian MLA is surgery, followed by adjuvant chemotherapy. Patients harboring pathogenic KRAS p.G12C mutations may benefit from targeted therapies. Ovarian MLA is an aggressive tumor, prone to recurrence in the short term, and has a poor prognosis.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To characterize multimodal metabolic disorders in subclinical Cushing's syndrome(SCS)patients with different cortisol levels,providing a reference for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical data of 165 SCS patients diagnosed at the First Medical Center of Chinese PLA General Hospital due to adrenal masses from January 2014 to October 2024.Using the serum cortisol levels after the midnight 1 mg dexamethasone suppression test(1 mg DST)as the cut-off point,SCS patients were divided into high-level group(1 mg DST-F>138 nmol/L,n=96)and low-level group(50 nmol/L<1 mg DST-F≤138 nmol/L,n=69).The differences in age,gender,body mass index(BMI),blood pressure,glucolipid metabolism indices,electrolytes,hormone levels,and imaging features of adrenal adenoma(such as CT values)were compared between the two groups.Multivariate linear regression was used to analyze the correlation between CT values and metabolic indices.Results Compared with low-level group,patients in high-level group were younger(54.0±11.3 vs.57.7±10.3,P=0.034),while there were no statistically significant differences in gender ratio or BMI between the two groups(P>0.05).Both groups exhibited decreased adrenocorticotropic hormone(ACTH)levels and disrupted circadian rhythm.Compared with low-level group,high-level group showed significantly higher F0:00 levels[250.00(170.07,422.53)nmol/L vs.110.00(82.74,133.90)nmol/L]and 24-hour urinary free cortisol(24 h UFC)[568.40(377.80,875.45)nmol/24 h vs.369.40(265.40,494.69)nmol/24 h](P<0.001),with no significant differences in serum F8:00,or 1 mg DST ACTH0:00 levels(P>0.05).Except for the fasting C-peptide level in the high-level group being higher than that in low-level group[(2.88±1.01)ng/ml vs.(2.46±0.78)ng/ml,P=0.024],there were no significant differences in blood pressure,blood lipids,glycated hemoglobin(HbA1c),fasting blood glucose,fasting insulin,serum electrolytes,uric acid,and other indices between the two groups(P>0.05).The CT value of adrenal adenoma during contrast-enhanced scanning was higher in high-level group[80.00(17.80,93.00)Hu vs.52.00(35.50,75.00)Hu,P=0.006]compared with low-level group.Multivariate linear regression analysis revealed that diastolic blood pressure was positively correlated with CT values of adrenal adenomas in both plain scanning(β=0.49,95%CI 0.09-0.90)and contrast-enhanced scanning(β=2.08,95%CI 0.76-3.39),while triglyceride levels were negatively correlated with plain scanning CT values(β=-5.77,95%CI-10.88--0.66).Conclusion Patients with SCS at different cortisol levels differ in age,fasting C-peptide levels,and CT values.CT values may serve as potential imaging markers to assess metabolic risk in SCS patients.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

The development of artificial intelligence(AI)technology has provided new avenues for the public to access health information.While both domestic and international research and practical applications of health conversational AI have emerged,there remains a lack of consensus on the key issues surrounding their development.Based on a comprehensive review of domestic and international literature and multiple rounds of expert consultations,the study focuses on six issues:the definition,characteristics,application scenarios,evaluation elements,evaluation methods,as well as prospects and challenges of AI-driven health consultation systems,and develops the practice guideline for health conversational artificial intelligence.The findings aim to provide scientific reference for promoting the innovative application of AI technology in the healthcare field.

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*