OBJECTIVES: To investigate the protective effects of graphene heating film far-infrared (FIR) hyperthermia therapy against frostbite in mice and its impacts on microcirculation and coagulation function. METHODS: Seventy-six C57BL/6J mice were randomized into control, model, graphene-FIR, and carbon fiber-FIR groups. After 7-day FIR intervention (4 h/day), the mice were subjected to acute (4 ℃, 4 h) and intermittent (4 ℃, 4 h/day for 3 days) cold exposure and the changes in rectal temperature were monitored. In liquid nitrogen frostbite experiment, 24 ICR mice were divided into model, graphene-FIR, and carbon fiber-FIR groups, and after a 7-day FIR pretreatment (4 h/day), the liquid nitrogen frostbite models were established and apparent scores of the wounds were assessed on days 3 and 6 after modeling. In carrageenan-induced thrombosis experiment, 40 ICR mice were allocated to control, model, graphene-FIR, carbon fiber-FIR, and prazosin groups to test the effect of a 7-day FIR intervention on thrombosis induced by intraperitoneal carrageenan injection (2.5 mg/kg) by measuring thrombus length, blood perfusion, and serum biomarkers (6-keto-PGF1α, TXB2, t-PA, IL-6, IL-1β, TNF‑α) 24 h after the injection. RESULTS: The mice in graphene-FIR group showed significantly elevated rectal temperature in cold exposure tests. In mice with liquid nitrogen-induced frostbite, graphene-FIR treatment significantly reduced the wound scores and reduced frostbite area, producing better effects than carbon fiber. In mice with carrageenan-induced thrombosis, graphene-FIR treatment significantly decreased tail thrombosis length and thrombosis area, increased blood perfusion, lowered serum levels of TXB2, TNF-α and IL-6, and increased the levels of 6-keto-PGF1α and t-PA. CONCLUSIONS Graphene heating film FIR therapy can alleviate frostbite injury in mice by improving microcirculation, suppressing thrombosis and inflammatory responses, and reducing coagulation dysfunction.
Animals ; Frostbite/therapy* ; Graphite ; Mice, Inbred C57BL ; Mice ; Infrared Rays ; Mice, Inbred ICR ; Hyperthermia, Induced/methods* ; Male ; Microcirculation

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
Animals ; Organoids/metabolism* ; Mice ; Humans ; Wound Healing ; Frostbite/metabolism* ; Skin/pathology* ; Induced Pluripotent Stem Cells/cytology* ; Cicatrix/pathology* ; Fibroblasts/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Extracellular Matrix/metabolism* ; Male

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Astragalus propinquus ; Frostbite/drug therapy*

Frostbite in Southwestern China has been overlooked due to its low incidence, relatively mild temperature and lack of literature published before. However, it needs to be further studied for religious diversity and distinct geomorphology. In this article, we reported an 18-year-old Tibetan girl who suffered from blizzard attack during pilgrimage. Her feet and several fingers showed mummified gangrene upon physical examination with poor movement. She was diagnosed with 3rd to 4th degree of frostbite. The girl was given oral ibuprofen, debridement and other regular treatment daily, but she was eventually amputated due to insufficient thrombolytic management in primary hospital, delayed informing consent in the referral hospital and ethnic conflict between religion and guidelines. This case enriched the experience of managing complex frostbite in Tibetan population and alarms that efforts should be integrated to protect pilgrims and mountaineers in the Tibetan region.
Adolescent ; Amputation ; China ; Female ; Frostbite/therapy* ; Humans ; Incidence ; Tibet

The human capacity for physiologic adaptation to cold is minimal. A cold environment can be a threat to the skin, leading to a subsequent fall in core body temperature. Many physiologic, behavioral, and environmental factors predispose to the global effects of cold injuries. Physical injuries caused by cold have two forms: systemic forms such as hypothermia and localized forms such as frostbite. Reduced temperature directly damages the tissue, as in frostbite and cold immersion foot. Vasospasm of vessels perfusing the skin induces chilblain, acrocyanosis, and frostbite. The degree of damage caused by cold is related to four factors: temperature, exposure time, wind intensity (temperature sensation), and high altitude.
Adaptation, Physiological ; Altitude ; Body Temperature ; Chilblains ; Cold Injury ; Frostbite ; Humans ; Hypothermia ; Immersion Foot ; Skin ; Wind

Monogenic autoimmune diseases (AD) present as lupus-like clinical manifestations with recurrent fever or various vasculopathies. Recurrent fever with an elevation of acute phase reactants and various skin lesions are similar in monogenic AD and autoinflammatory disease. The molecular pathogenesis of adult systemic erythematosus can be understood through monogenic AD based on gene defects: complement, apoptosis, interferonopathy via nucleic acid sensing, tolerance, rasopathies, and others. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common occurrences in type I interferonopathy. Some syndromes have been reported to present with autoimmune inflammation and the general clinical findings, including cerebral calcification. Various clinical manifestations in monogenic AD present in accordance with the gene loss- or gain-of-function mutations involved. The monogenic AD for the early onset of more severe lupus-like symptoms or vasculopathy needs to be considered. Furthermore, clinical trials were conducted via targeted therapy for related molecular pathways, because conventional treatments were not effective in managing monogenic AD.
Acute-Phase Proteins ; Adult ; Apoptosis ; Autoimmune Diseases* ; Chilblains ; Complement System Proteins ; Fever ; Humans ; Inflammation ; Interferons ; Livedo Reticularis ; Lung Diseases, Interstitial ; Lupus Erythematosus, Systemic ; Panniculitis ; Skin

Frostbite is a common disease in winter, and systemic or local injury caused by low temperature invasion. Frostbite sites are commonly face, ears, nose, hands, feet and other peripheral blood circulation parts. The main symptoms are pale skin, cold, pain and numbness, skin itching in high temperature, and severe cases may suffer from skin erosions and ulcers. Frostbite model is a pathological model mainly based on Western medicine index. Based on the analysis of clinical symptoms of frostbite in traditional Chinese medicine and western medicine, and a large number of experimental studies on the existing animal models, the animal model preparation of specifications (draft) was formulated as follows.
Animals ; Cold Temperature ; Frostbite ; Models, Animal

A 39-year-old Caucasian man was referred to University Hospital Salamanca from a primary care unit due to the presence of an erythematous violaceous nodule at the superior portion of his nose. Physical examination indicated that the firm, fixed erythematous violaceous nodule measured approximately 2 cm in diameter and was located inferior to a scar on the nasal bridge. Cutaneous involvement in sarcoidosis occurs in 25% of cases. A wide range of clinical presentations of cutaneous sarcoidosis is recognized. Skin lesions are classified as either non-specific, of which erythema nodosum is the most representative and specific, or as granulomatous, which includes maculopapular nodules, plaques, infiltrated scars, lupus pernio, ulcerations, warty lesions and erythroderma. Scar sarcoidosis is a type of cutaneous sarcoidosis.
Adult ; Chilblains ; Cicatrix ; Dermatitis, Exfoliative ; Erythema Nodosum ; Humans ; Nose ; Physical Examination ; Primary Health Care ; Sarcoidosis* ; Skin ; Ulcer

No abstract available.
Chilblains*

Squamous cell carcinoma commonly originates from recalcitrant wound sites, including burn scars, pressure sores, stasis ulcers, osteomyelitis, and sites of frostbite. A 62-year-old male was referred to the dermatology department for skin necrosis of his right great toe and walking difficulty. He had a history of smoking, drinking alcohol, and frostbite of his right great toe 9 years prior, which deteriorated into osteomyelitis due to poor care. Although a skin biopsy was recommended before amputation, the two procedures were performed simultaneously due to a lack of toe function due to severe osteolysis. Biopsy of the amputated toe tip showed many lobules consisting of atypical keratinocytes with hyperchromatic nuclei, and severe dermal pleomorphism. After evaluation for distant metastasis, including a (99m) Tc-MDP bone scan, 18F-FDG positron emission tomography scan, computed tomography, and ultrasound, no metastasis was detected.
Amputation ; Biopsy ; Burns ; Carcinoma, Squamous Cell* ; Cicatrix ; Dermatology ; Drinking ; Fluorodeoxyglucose F18 ; Frostbite ; Humans ; Keratinocytes ; Male ; Middle Aged ; Necrosis ; Neoplasm Metastasis ; Osteolysis ; Osteomyelitis* ; Positron-Emission Tomography ; Pressure Ulcer ; Skin ; Smoke ; Smoking ; Toes ; Ultrasonography ; Varicose Ulcer ; Walking ; Wounds and Injuries