A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.

ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population aging. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.
Humans ; Male ; Female ; Incidence ; Fractures, Bone/epidemiology* ; Middle Aged ; Adult ; Global Health ; Aged ; Global Burden of Disease ; Adolescent ; Child ; Young Adult ; Foot Injuries/epidemiology* ; Cost of Illness ; Child, Preschool ; Aged, 80 and over ; Infant

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

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

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.