Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.

Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

Upon penetration into the host organism,the decapsulated larvae(intestinal infective stage 1 larvae)of Trichinella spiralis(T.spiralis)proceed to invade the host's small intestinal epithelial cells to continue their development,which is a critical step for T.spiralis infection and pathogenesis.Based on our prior research,the Ts-DNase Ⅱ-7 protein,which is present in the adult stage of T.spiralis,has a role in promoting the parasite's invasion of the intestinal epithelium.This is achieved by disrupting the integrity of the intestinal barrier,consequently promoting the parasitization of these cells in the host organism.Ts-DNase Ⅱ-7 can induce differential expression of various miRNAs,among which miR-142-5p has been reported to be involved in disrupting the intestinal barrier.Therefore,in this study,we investigated the mechanism by which Ts-DNase Ⅱ-7-induced miR-142-5p regulates intestinal epithelial cell barrier function by affecting target genes.The experiment was divided into Ts-DNase Ⅱ-7-treated group,miR-142-5p overexpression group(OE),miR-142-5p inhibition group(Inhibition),negative control group(NC)and control group(Control),lentiviral vectors for overexpression and suppression of miR-142-5p expression were used to infect human colorectal adenocarcinoma cells Caco-2 at an MOI of 80,and puromycin(8 mg/L)was used to screen cells to obtain cell lines that stably suppressed the expression of miR-142-5p and cell lines that miR-142-5p was overexpressed,cell transfection efficiency was assessed by fluorescence microscopy,and the relative expression of miR-142-5p was detected by RT-qPCR in each group of cells.The target gene Claudin-1(CLDN1)was predicted and validated using miR target prediction database,RT-qPCR,Western blot and dual luciferase assay.HE staining,Western blot and quantitative analysis of monolayer transmembrane electrical resistance(TEER)and FITC permeability were then applied to elucidate the mechanism of action of miR-142-5p.Caco-2 cells were lentivirally infected and successful transfection was verified by fluorescence microscopy and RT-qPCR.Dual luciferase and Western blot results showed that CLDN1 was a direct target gene of miR-142-5p(P＜0.001).Compared to the Ts-DNaseⅡ-7 alone treatment group and the OE+Ts-DNase Ⅱ-7 group,the miR-142-5p inhibited expression group and alleviated Ts-DNase Ⅱ-7-induced down-regulation of CLDN1 mRNA and protein levels(P＜0.01 and P＜0.05,respectively)and re-versed the decrease in TEER and elevated permeability(P＜0.01).Ts-DNase Ⅱ-7 up-regulates miR-142-5p expression,causing reduced CLDN1 expression and impaired intestinal barrier function in Caco-2 monolayer cells,which in turn promotes T.spiralis invasion of the intestinal epithelium to achieve further development.

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

Objective:To investigate the clinical efficacy of oxcarbazepine versus carbamazepine combined with baclofen in the treatment of trigeminal neuralgia. Methods:A total of 74 patients with trigeminal neuralgia who received treatment in Haiyang People's Hospital from May 2019 to May 2021 were prospectively included in this study. They were randomly divided into an observation group and a control group ( n = 37 per group). The observation group was treated with oxcarbazepine combined with baclofen, while the control group was treated with carbamazepine combined with baclofen. Both groups were treated for 4 successive weeks. Clinical efficacy, adverse reactions, Visual Analogue Scale (VAS) scores before and after treatment, levels of pain transmitters [substance P (SP), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP)], and quality of life were compared between the two groups. Results:The total effective rate in the observation group was 97.3% (36/37), which was significantly higher than 83.8% (31/37) in the control group (χ 2 = 3.95, P < 0.05). Before treatment, there were no significant differences in VAS score, SP, 5-HT, β-EP levels, and EQ-5D Health-Related Quality of Life Questionnaire (EQ-5D) score between the two groups (all P > 0.05). After treatment, VAS score, SP, 5-HT levels, and EQ-5D score in each group were significantly decreased compared with those before treatment. After treatment, VAS score, SP and 5-HT levels in the observation group were significantly lower than those in the control group [(3.1±0.8) points vs. (4.2±0.9) points, (240.1 ± 34.1) ng/L vs. (314.1±40.1) ng/L, (38.2 ± 6.1) ng/L vs. (52.1±9.1) ng/L, all P < 0.001]. After treatment, β-EP level in each group was significantly increased compared with that before treatment ( P < 0.001). After treatment, β-EP level in the observation group was significantly higher than that in the control group [(268.1 ± 38.1) ng/L vs. (214.1 ± 29.0) ng/L, P < 0.001]. After treatment, EQ-5D scores in the observation group were significantly lower than those in the control group (all P < 0.001). There was no significant difference in incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Oxcarbazepine combined with baclofen has superior efficacy in the treatment of trigeminal neuralgia to carbamazepine combined with baclofen. The former can more obviously relieve pain, reduce pain neurotransmitter levels, improve quality of life, and has less adverse reactions.

OBJECTIVE: To investigate the accuracy, safety, and short-term effectiveness of a domestic robot-assisted system in total knee arthroplasty (TKA) by a multicenter randomized controlled trial. METHODS: Between December 2021 and February 2023, 138 patients with knee osteoarthritis who received TKA in 5 clinical centers were prospectively collected, and 134 patients met the inclusion criteria were randomly assigned to either a trial group ( n=68) or a control group ( n=66). Seven patients had lost follow-up and missing data, so they were excluded and the remaining 127 patients were included for analysis, including 66 patients in the trial group and 61 patients in the control group. There was no significant difference ( P>0.05) in gender, age, body mass index, side, duration of osteoarthritis, Kellgren-Lawrence grading, preoperative Knee Society Score (KSS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between the two groups. The trial group completed the TKA by domestic robot-assisted osteotomy according to the preoperative CT-based surgical planning. The control group was performed by traditional osteotomy plate combined with soft tissue release. Total operation time, osteotomy time of femoral/tibial side, intraoperative blood loss, and postoperative complications were recorded and compared between the two groups. The radiographs were taken at 5 and 90 days after operation, and hip-knee-ankle angle (HKA), lateral distal angle of femur (LDFA), and posterior tibial slope (PTS) were measured. The difference between the measured values of the above indexes at two time points after operation and the preoperative planning target values was calculated, and the absolute value (absolute error) was taken for comparison between the two groups. The postoperative recovery of lower limb alignment was judged and the accuracy was calculated. KSS score and WOMAC score were used to evaluate the knee joint function of patients before operation and at 90 days after operation. The improvement rates of KSS score and WOMAC score were calculated. The function, stability, and convenience of the robot-assisted system were evaluated by the surgeons. RESULTS: The total operation time and femoral osteotomy time of the trial group were significantly longer than those of the control group ( P<0.05). There was no significant difference in the tibial osteotomy time and the amount of intraoperative blood loss between the two groups ( P>0.05). The incisions of both groups healed by first intention after operation, and there was no infection around the prosthesis. Nine patients in the trial group and 8 in the control group developed lower extremity vascular thrombosis, all of which were calf intermuscular venous thrombosis, and there was no significant difference in the incidence of complications ( P>0.05). All patients were followed up 90 days. There was no significant difference in KSS score and WOMAC score between the two groups at 90 days after operation ( P>0.05). There was significant difference in the improvement rate of KSS score between the two groups ( P<0.05), while there was no significant difference in the improvement rate of WOMAC score between the two groups ( P>0.05). Radiological results showed that the absolute errors of HKA and LDFA in the trial group were significantly smaller than those in the control group at 5 and 90 days after operation ( P<0.05), and the recovery accuracy of lower limb alignment was significantly higher than that in control group ( P<0.05). The absolute error of PTS in the trial group was significantly smaller than that in the control group at 5 days after operation ( P<0.05), but there was no significant difference at 90 days between the two groups ( P>0.05). The functional satisfaction rate of the robot-assisted system was 98.5% (65/66), and the satisfaction rates of stability and convenience were 100% (66/66). CONCLUSION Domestic robot-assisted TKA is a safe and effective surgical treatment for knee osteoarthritis, which can achieve favorable lower limb alignment reconstruction, precise implant of prosthesis, and satisfactory functional recovery.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Blood Loss, Surgical ; Robotics ; Knee Joint/surgery* ; Knee Prosthesis ; Retrospective Studies

Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.