Objective To evaluate the efficacy and safety of a novel gastrointestinal mucosal elevation gel in vivo porcine model. Methods Eight healthy white pigs were selected, which were uesd to bump height evaluation (n=2) and safety evaluation (n=6). The sample (alimentary canal mucosa bump gel sample) and the control sample (disposable endoscopic submucosal filler of alimentary canal) were respectively injected into the submucosa of pig gastric antrum and gastric body. In the evaluation of elevation height, the morphology, persistence, and clinical safety of mucosal elevation were observed and recorded immediately and 30 minutes after injection. In safety evaluation, endoscopic mucosal resection was performed after injection, and the mucosal protrusion shape, product efficacy, and clinical safety were observed and recorded at immediate and 7-day time points. After observation, all animals were euthanized and tissue samples were collected and excised for histopathological evaluation. Results In elevation height evaluation, sample group showed a steep elevation immediately after surgery, exhibiting a more pronounced elevation morphology compared to control group (P=0.019). Only two (25%) sites of the elevation showed slight collapse in 30 minutes after surgery, and the durability notably increased compared to control group (8 all collapsed, P＜0.001). In safety evaluation, the average trauma area of sample group was 1.77 mm², which was significantly lower than control group (2.65 mm², P＜0.001). There was no statistical difference among average injection dose per unit area, surgical time per unit area, and en bloc resection rate. Sample group showed mild ulcers and only 1 (12.5%) site of mild bleeding at immediate time point after surgery. No bleeding, perforation, ulcer or edema was observed in sample group 7 days after surgery, and no statistical difference was identified compared to control group. Histopathological evaluation found that the gastric antrum and body tissues exhibited moderate injury and mild edema at immediate time point, accompanied by mild inflammatory cellular infiltration. At 7-day time point, gastric antrum tissues demonstrated moderate injury, mild edema and mild inflammatory cellular infiltration, with 1 (12.5%) site of tissues infected, while in gastric body tissues, no bleeding was observed, whereas moderate injury and mild edema were evident, accompanied by mild inflammatory cellular infiltration and 3 (37.5%) sites of tissues infected, all of which were not statistically different from control group. Conclusion The novel gastrointestinal mucosal elevation gel exhibited steep elevation morphology, long-lasting elevation height, and favorable efficacy and safety in preclinical animal trials, showing enormous clinical application potential.

Objective:To investigate the diagnostic efficacy of intraoperative direct sonication in periprosthetic joint infection (PJI).Methods:This is a retrospective case series study. The clinical data of 490 patients with PJI or aseptic prosthesis loosening after hip or knee arthroplasty admitted to the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2023 were retrospectively analyzed. There were 209 male cases, 281 female cases, aged ( M(IQR)) 63 (19) years (range: 15 to 89 years). There were 328 cases of PJI (123 cases of traditional sonication, 205 cases of intraoperative direct sonication, and 204 cases had simultaneous intraoperative synovial fluid), and 162 patients of aseptic loosening (89 cases of traditional sonication, 73 cases of intraoperative direct sonication, and 96 cases had simultaneous intraoperative synovial fluid). The method of traditional sonication: the prosthesis components were placed in a sterile container, vortexed for 30 seconds, then placed in an ultrasound bath to sonication (frequency:(40±2) kHz, power density:(0.22±0.04) W/cm2) for 5 minutes, vortexed again for 30 seconds, and the resulting sonicate fluid was extracted for culture. The method of intraoperative direct sonication: during the operation, the surgical area, the prosthesis and the tissues around the prosthesis which were placed in a sterile container were respectively subjected to sonication for 5 minutes using a portable handheld ultrasonic cell disruptor device (frequency: 25 kHz, power density:(0.22±0.04) W/cm2), and the fluids before and after sonication were extracted for culture. The method of intraoperative synovial fluid: during the operation, the joint capsule was incised, and the synovial fluid was extracted under direct vision for culture. The sensitivity, specificity, positive and negative predictive values, Youden index, the effect of preoperative antimicrobial agents on culture results, and culture duration for different culture methods. Receiver operating characteristic (ROC) curves were plotted, and the diagnostic efficacy of these methods for PJI was compared using the χ2 test, the Wilcoxon signed-rank test, and other appropriate statistical methods. Results:The sensitivity of intraoperative direct sonication was significantly higher than that of intraoperative synovial fluid culture (89.8%(184/205) vs.56.9%(116/204), χ2=44.457, P<0.01) and traditional sonication (89.8%(184/205) vs.66.7%(82/123), χ2=121.588, P<0.01). However, its specificity was lower compared to intraoperative synovial fluid (87.5%(64/73) vs. 99.0%(95/96), χ2=9.491, P=0.002). The culture duration for intraoperative direct sonication was shorter than for intraoperative synovial fluid 87.0 (41.8) hours vs. 112.5 (78.5) hours, Z=-5.121, P<0.01) and traditional sonication (87.0 (41.8) hours vs. 119.0 (67.5) hours, Z=-7.119, P<0.01). Gram-positive bacteria (predominantly Staphylococcus aureus and Staphylococcus epidermidis) were the most common isolates across all three culture methods. Furthermore, intraoperative direct sonication was more likely to detect polymicrobial infections compared to traditional sonication (38.6% vs. 2.4%, χ2=37.223, P<0.01) and intraoperative synovial fluid (38.6% vs. 0.9%, χ2=55.527, P<0.01). The ROC curve revealed that the area under the curve of intraoperative direct sonication,intraoperative synovial fluid culture and traditional sonication were 0.886 (95% CI:0.843 to 0.930), 0.779 (95% CI:0.743 to 0.815) and 0.788 (95% CI: 0.736 to 0.839). Conclusions:Compared with intraoperative synovial fluid and traditional sonication, intraoperative direct sonication has excellent sensitivity, the shortest appropriate culture duration for pathogenic bacteria, and it is more likely to diagnose PJI patients with polymicrobial infections, having better diagnostic efficacy in the diagnosis of PJI.

Objective To develop a Self-Report Scale of Symptoms for Post Intensive Care Syndrome-Family(PICS-F)and validate its reliability and validity,providing a scientific tool for healthcare professionals to comprehensively assess post intensive care syndrome-family.Methods Based on the symptom experience dimension of Symptom Management Theory,a preliminary version of the scale was developed through literature analysis,semi-structured interviews,expert consultations,and a pilot survey.A convenience sampling method was used to conduct the pre-trial version of the scale questionnaire survey on 442 family members of ICU patients at a tertiary A comprehensive hospital in Wuhan from June to September 2024.The test of the validity and reliability was conducted.Results The developed scale consists of 4 dimensions and 20 items.Exploratory factor analysis identified 4 factors,with a cumulative variance contribution rate of 70.921％.The content validity index at the scale level was 0.941,and the content validity indices for individual items ranged from 0.809 to 1.000.Confirmatory factor analysis indicated that the model fit indices were within acceptable ranges.The overall Cronbach's αcoefficient for the scale was 0.941,and the split-half reliability was 0.832.Conclusion The Self-Report Scale of Symptoms for PICS-F demonstrates good reliability and validity.It can comprehensively reflect the primary symptoms of PICS-F,and can serve as an effective measurement tool for clinicians to assess PICS-F in family members of ICU patients.

Objective To develop a Self-Report Scale of Symptoms for Post Intensive Care Syndrome-Family(PICS-F)and validate its reliability and validity,providing a scientific tool for healthcare professionals to comprehensively assess post intensive care syndrome-family.Methods Based on the symptom experience dimension of Symptom Management Theory,a preliminary version of the scale was developed through literature analysis,semi-structured interviews,expert consultations,and a pilot survey.A convenience sampling method was used to conduct the pre-trial version of the scale questionnaire survey on 442 family members of ICU patients at a tertiary A comprehensive hospital in Wuhan from June to September 2024.The test of the validity and reliability was conducted.Results The developed scale consists of 4 dimensions and 20 items.Exploratory factor analysis identified 4 factors,with a cumulative variance contribution rate of 70.921％.The content validity index at the scale level was 0.941,and the content validity indices for individual items ranged from 0.809 to 1.000.Confirmatory factor analysis indicated that the model fit indices were within acceptable ranges.The overall Cronbach's αcoefficient for the scale was 0.941,and the split-half reliability was 0.832.Conclusion The Self-Report Scale of Symptoms for PICS-F demonstrates good reliability and validity.It can comprehensively reflect the primary symptoms of PICS-F,and can serve as an effective measurement tool for clinicians to assess PICS-F in family members of ICU patients.

Objective:To investigate the diagnostic efficacy of intraoperative direct sonication in periprosthetic joint infection (PJI).Methods:This is a retrospective case series study. The clinical data of 490 patients with PJI or aseptic prosthesis loosening after hip or knee arthroplasty admitted to the Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2023 were retrospectively analyzed. There were 209 male cases, 281 female cases, aged ( M(IQR)) 63 (19) years (range: 15 to 89 years). There were 328 cases of PJI (123 cases of traditional sonication, 205 cases of intraoperative direct sonication, and 204 cases had simultaneous intraoperative synovial fluid), and 162 patients of aseptic loosening (89 cases of traditional sonication, 73 cases of intraoperative direct sonication, and 96 cases had simultaneous intraoperative synovial fluid). The method of traditional sonication: the prosthesis components were placed in a sterile container, vortexed for 30 seconds, then placed in an ultrasound bath to sonication (frequency:(40±2) kHz, power density:(0.22±0.04) W/cm2) for 5 minutes, vortexed again for 30 seconds, and the resulting sonicate fluid was extracted for culture. The method of intraoperative direct sonication: during the operation, the surgical area, the prosthesis and the tissues around the prosthesis which were placed in a sterile container were respectively subjected to sonication for 5 minutes using a portable handheld ultrasonic cell disruptor device (frequency: 25 kHz, power density:(0.22±0.04) W/cm2), and the fluids before and after sonication were extracted for culture. The method of intraoperative synovial fluid: during the operation, the joint capsule was incised, and the synovial fluid was extracted under direct vision for culture. The sensitivity, specificity, positive and negative predictive values, Youden index, the effect of preoperative antimicrobial agents on culture results, and culture duration for different culture methods. Receiver operating characteristic (ROC) curves were plotted, and the diagnostic efficacy of these methods for PJI was compared using the χ2 test, the Wilcoxon signed-rank test, and other appropriate statistical methods. Results:The sensitivity of intraoperative direct sonication was significantly higher than that of intraoperative synovial fluid culture (89.8%(184/205) vs.56.9%(116/204), χ2=44.457, P<0.01) and traditional sonication (89.8%(184/205) vs.66.7%(82/123), χ2=121.588, P<0.01). However, its specificity was lower compared to intraoperative synovial fluid (87.5%(64/73) vs. 99.0%(95/96), χ2=9.491, P=0.002). The culture duration for intraoperative direct sonication was shorter than for intraoperative synovial fluid 87.0 (41.8) hours vs. 112.5 (78.5) hours, Z=-5.121, P<0.01) and traditional sonication (87.0 (41.8) hours vs. 119.0 (67.5) hours, Z=-7.119, P<0.01). Gram-positive bacteria (predominantly Staphylococcus aureus and Staphylococcus epidermidis) were the most common isolates across all three culture methods. Furthermore, intraoperative direct sonication was more likely to detect polymicrobial infections compared to traditional sonication (38.6% vs. 2.4%, χ2=37.223, P<0.01) and intraoperative synovial fluid (38.6% vs. 0.9%, χ2=55.527, P<0.01). The ROC curve revealed that the area under the curve of intraoperative direct sonication,intraoperative synovial fluid culture and traditional sonication were 0.886 (95% CI:0.843 to 0.930), 0.779 (95% CI:0.743 to 0.815) and 0.788 (95% CI: 0.736 to 0.839). Conclusions:Compared with intraoperative synovial fluid and traditional sonication, intraoperative direct sonication has excellent sensitivity, the shortest appropriate culture duration for pathogenic bacteria, and it is more likely to diagnose PJI patients with polymicrobial infections, having better diagnostic efficacy in the diagnosis of PJI.

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

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 diagnostic value of erythrocyte sedimentation rate/C-reactive protein (ECR), fibrinogen and D-dimer in periprosthetic infection after artificial knee replacement.Methods:A total of 205 patients, including 62 males and 143 females, aged 66.9±9.5 years (range 26-84 years), who underwent revision of artificial knee joint at Department of Joint Surgery, The First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2021 were retrospectively collected.122 cases of periprosthetic joint infection (PJI), including 43 cases of acute infection; 79 cases of chronic infection (13 cases of chronic infection combined with rheumatoid arthritis were analyzed separately); there were 83 cases without PJI, including 73 cases of aseptic loosening, 8 cases of prosthesis dislocation and 2 cases of joint stiffness. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, fibrinogen and D-dimer levels were examined before surgery, and the sensitivity and specificity of the indicators were calculated using the receiver operating characteristic (ROC) curve. The diagnostic value of different inflammatory markers was compared according to the area under curve (AUC).Results:The levels of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in acute PJI group were 2.47±2.91, 50 (38, 62) mm/1 h, 31.6 (13.9, 79.3) mg/L, 4.25±0.94 g/L, 763 (453, 1 157) ng/ml, respectively. The chronic PJI group was 3.06±2.95, 50 (34, 64) mm/1 h, 20.4(12.7, 43.3) mg/L, 4.19±0.91 g/L, 586 (317, 1 122) ng/ml, and the non-PJI group was 6.20±4.64, 22 (15, 34) mm/1 h, 4.6 (2.7, 7.74) mg/L, 3.10±0.59 g/L and 363 (181, 591)ng/ml were statistically significant ( P<0.05). The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in the acute PJI group were 0.82, 0.85, 0.90, 0.88, and 0.76, respectively.The optimal critical values were 2.89, 37.00 mm/1 h, 13.6 mg/L, 3.86 g/L, and 443.0 ng/ml, respectively, with sensitivity of 76.7%, 79.1%, 76.7%, 69.8%, and 82.4%, and specificity of 79.5%, 78.3%, 94.0%, 94.0%, 90.4%, and 63.8%, respectively. The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, D-dimer, and white blood cell count in the chronic PJI group were 0.77, 0.82, 0.87, 0.85, 0.67, and 0.63, respectively. The optimal critical values are 2.91, 33.00 mm/1 h, 10.9 mg/L, 4.01 g/L, 558.5 ng/ml, and 5.575×10 9 /L, respectively, with sensitivity of 68.2%, 78.8%, 81.8%, 63.6%, 57.9%, and 75.8%, and specificity of 79.5%, 73.5%, 88.0%, 95.2%, 72.5%, and 49.4%, respectively. Conclusion:Fibrinogen has a higher diagnostic value for knee joint PJI, followed by ECR, and D-dimer has the lowest diagnostic value for knee joint PJI.

Objective:To investigate the gender differences in serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), fibrinogen (FIB) and D-dimer for the diagnosis of chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision arthroplasty in the Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to gender and diagnosis, they were divided into four groups: 78 cases of male chronic PJI, 108 cases of male aseptic loosening, 95 cases of female chronic PJI, and 189 cases of female aseptic loosening. The serological results of CRP, ESR, PLT, FIB and D-dimer were collected before operation. The receiver operating characteristics (ROC) curves were used to determine the optimal cut-off values of CRP, ESR, PLT, FIB and D-dimer for the diagnosis of chronic PJI in different genders, and to calculate their sensitivity and specificity. The diagnostic efficacy of the index was analyzed by comparing the area under curve (AUC) of different indicators.Results:The levels of ESR, PLT and D-dimer in the male chronic PJI group were 43 (20.0, 52.5) mm/1 h, 249×10 9 (204×10 9, 306×10 9) /L, 449 (219,833) μg/L, respectively, which were lower than those in the female group of 56 (40, 65) mm/1 h, 295×10 9 (228×10 9, 364×10 9) /L, and 645 (345, 1 157) μg/L, with statistically significant differences ( Z=-4.17, P<0.001; Z=-2.17, P=0.030; Z=-2.82, P=0.005). The AUC of CRP in the male chronic PJI group was 0.841, which was higher than the AUC of the other four indicators; CRP was combined with ESR, PLT, FIB and D-dimer to establish a joint prediction model for male chronic PJI. The ROC curve showed that the combination of CRP+FIB had a maximum AUC [0.849, 95% CI (0.79, 0.91)], sensitivity of 80% and specificity of 86%. The AUC of CRP in the female chronic PJI group was 0.866, which was higher than the AUC of the other four indices; CRP was combined with ESR, PLT, FIB and D-dimer to establish a combined prediction model for female chronic PJI. The ROC curve showed that the combination of CRP+PLT had the maximum AUC [0.883, 95% CI (0.84, 0.93)], sensitivity of 87% and specificity of 79%. Conclusion:Serologic indicators in patients with chronic PJI are gender-specific. CRP combined with FIB has the highest diagnostic value for the chronic PJI in males, while CRP combined with PLT has the highest diagnostic value for the chronic PJI in females.

Objective:To investigate the diagnostic value of plasma fibrinogen (FIB) in chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision hip and knee arthroplasty after primary hip and knee arthroplasty in the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to the diagnosis of the disease, 173 patients (112 hips and 61 knees) were divided into chronic PJI group, including 78 males and 96 females, aged 65 (53, 72) years; and 297 patients (216 hips and 81 knees) were divided into aseptic loosening group, including 108 males and 189 females, aged 63 (50, 72) years. The preoperative levels of FIB, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer and platelet were compared between the two groups, and the sensitivity and specificity of the diagnosis of chronic PJI were calculated. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of FIB, CRP, ESR, platelet and D-dimer for the diagnosis of chronic PJI. The diagnostic efficacy of each indicator was analyzed by comparing the area under curve (AUC) and using a combined diagnostic test.Results:FIB, CRP, ESR, platelets and D-dimer in the chronic PJI group were 4.05 (3.52, 4.72) g/L, 19.5 (10.7, 40.0) mg/L, 50 (28, 60) mm/1 h, 270 (221, 351)×10 9 /L, 514 (261, 873) μg/L, respectively, which were higher than 3.25 (2.80, 3.63) g/L, 3.7 (2.0, 6.7) mg/L, 20 (12, 30) mm/1 h, 225 (182, 269)×10 9 /L, and 310 (167, 569) μg/L in sterile loosening group, with statistically significant differences ( P<0.05). The AUC of FIB, CRP, ESR, platelets and D-dimer in the diagnosis of chronic PJI were 0.78 (95% CI: 0.73, 0.82), 0.86 (95% CI: 0.82, 0.89), 0.80 (95% CI: 0.76, 0.85), 0.68 (95% CI: 0.63, 0.73), 0.64 (95% CI: 0.59, 0.69); the optimal cut-off values were 3.73 g/L, 9.64 mg/L, 39 mm/1 h, 280×10 9 /L, 624 μg/L; the sensitivity was 68%, 79%, 69%, 47%, 43%; the specificity was 81%, 85%, 85%, 81%, 79%, respectively. When CRP, ESR, FIB, platelets and D-dimer were combined sequentially to diagnose patients with chronic PJI, the sensitivity and specificity of the series test were 12.7% and 99.7%, and those of the parallel test were 100% and 37.3%. The combined diagnostic test showed that the maximum AUC of FIB combined with CRP was 0.85 (95% CI: 0.81, 0.89), with a sensitivity of 76% and a specificity of 89%. Conclusion:The clinical value of plasma FIB in the diagnosis of chronic PJI is not superior to that of CRP and ESR, but the combination of FIB and CRP can improve the specificity.