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

OBJECTIVE: A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). METHODS: Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. RESULTS: There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). CONCLUSION The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Aged ; Female ; Humans ; Male ; Middle Aged ; Anesthesia, Local/methods* ; Anesthetics, Local/administration & dosage* ; Arthroplasty, Replacement, Knee/methods* ; Bupivacaine/administration & dosage* ; Liposomes ; Osteoarthritis, Knee/surgery* ; Pain Measurement ; Pain, Postoperative/prevention & control* ; Prospective Studies ; Treatment Outcome

Objective:To investigate the role of rapamycin target protein (mTOR) in lanthanum-induced injury of cerebral cortical neurons in offspring rats, and the effect on brain development, learning and memory ability of offspring rats.Methods:Thirty-two adult female and 32 male Wistar rats, were randomly divided into 4 groups according to their body weight, with 16 rats in each group (half female and half male). Female rats were fed with different amounts of lanthanum chloride[0.0 (control), 2.5, 5.0, 10.0 g/L], while male rats drank normal water. Female and male rats were mated in cages at a ratio of 1∶1. Female rats began to be exposed to lanthanum from pregnancy, while their offspring were exposed to lanthanum until 4 weeks after weaning. Morris water maze experiment was carried out in the 4 groups of offspring rats, and the effects of lanthanum on learning and memory were observed by space exploration. The cerebral cortex of offspring rats was taken, and the amount of Nissl body was observed under microscope after Nissl staining. The expression of mTOR mRNA in offspring rats cerebral cortex nerve cells was measured by real-time quantitative PCR. Western blotting was used to detect the protein content of p-mTOR in offspring rats cortical neurons.Results:Compared with the control group, the body weight of offspring rats exposed to lanthanum at 2.5, 5.0 and 10.0 g/L was significantly decreased [(121.75 ± 11.20), (110.00 ± 11.59), (98.88 ± 7.95) and (85.63 ± 7.25) g, P < 0.05], and the brain tissue coefficient and cortical coefficient were significantly increased [(1.43 ± 0.10)%, (1.56 ± 0.18)%, (1.66 ± 0.14)%, (1.89 ± 0.16)%; (0.86 ± 0.08)%, (0.94 ± 0.08)%, (1.01 ± 0.07)%, (1.08 ± 0.09)%, P < 0.05]. The brain weight [(1.63 ± 0.05), (1.61 ± 0.03) g] of 5.0 and 10.0 g/L lanthanum-exposed groups were significantly lower than those in the control group and 2.5 g/L lanthanum-exposed group [(1.73 ± 0.06), (1.70 ± 0.06) g, P < 0.05]. Compared with the control group (53.25 ± 9.93), the amounts of Nissl body in cerebral cortical neurons in different lanthanum-exposed groups (36.13 ± 3.98, 27.50 ± 5.21, 13.63 ± 5.93) were significantly decreased ( P < 0.05). The results of space exploration experiment showed that compared with the control group [(5.75 ± 1.98) times, (10.69 ± 2.96) s, (3.75 ± 1.28) times], the times of entering the target quadrant [(3.63 ± 1.41) times] and the stay time in the target quadrant [(5.12 ± 2.09) s] in 10.0 g/L lanthanum-exposed group were significantly reduced ( P < 0.05), and the times of entering the platform [(1.88 ± 0.84), (1.13 ± 1.12) times] in 5.0 and 10.0 g/L lanthanum-exposed groups were significantly reduced ( P < 0.05). There were significant differences in mTOR mRNA (1.00 ± 0.28, 0.74 ± 0.19, 0.58 ± 0.13, 0.45 ± 0.29) and p-mTOR protein expression levels (0.69 ± 0.07, 0.33 ± 0.06, 0.30 ± 0.04, 0.17 ± 0.03) in cortical tissues ( F = 8.33, 139.12, P < 0.05). Conclusion:Lanthanum exposure can damage cortical neurons, affect the brain development of offspring rats, reduce the expression of mTOR mRNA and p-mTOR protein in the brain of offspring rats, reduce the ability of space exploration and observation, resulting in the decline of learning and memory ability of offspring rats.

Sixty-three cases of neurodermatitis were treated with seven-star needle, tapping the affected area until slight bleeding and then ignite moxa-stick to make lsft-right repeated rotation moxibustion about 2 cm away from the skin. The total effective rate was 100% after three treatment course.

Semi-purified diets containing 30 ppm or 500 ppm dl-?-tocopherol (VE) were fed for 8 weeks to young (3 months) and old (18 months) Swiss mice. The blastogenic response of splenocytes as well as serum VE and lipid peroxides (LPO) in livers were measued. The results showed that the old mice fed 500 ppm VE had a significantly higher serum VE level and blastogenic response of splenocytes to Con A and LPS than those fed 30 ppm VE (p