1.Preclinical efficacy and safety evaluation of a novel gastrointestinal mucosal elevation gel in vivo porcine model
Yicheng TIAN ; BAHETINUER JIASHAER ; Yan ZHU ; Wei XIA ; Pinghong ZHOU ; Mingyan CAI
Chinese Journal of Clinical Medicine 2025;32(5):768-775
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.
2.Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear.
Jieyu QI ; Wenjuan HUANG ; Yicheng LU ; Xuehan YANG ; Yinyi ZHOU ; Tian CHEN ; Xiaohan WANG ; Yafeng YU ; Jia-Qiang SUN ; Renjie CHAI
Neuroscience Bulletin 2024;40(1):113-126
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
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Humans
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Hair Cells, Auditory, Inner/physiology*
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Ear, Inner/physiology*
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Hair Cells, Auditory/physiology*
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Regeneration/genetics*
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Stem Cells
3.The diagnostic value of some inflammatory markers for knee joint periprosthetic joint infection
Jujie TIAN ; Li CAO ; Yicheng LI ; Xiaobin GUO ; Xiaogang ZHANG
Chinese Journal of Orthopaedics 2023;43(11):751-758
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.
4.Gender differences in serological indicators for the diagnosis of chronic periprosthetic infections
Shuaifei TIAN ; Xiaobin GUO ; Wulamu WUHUZI· ; Yushan NUERAIJIANG· ; Yicheng LI ; Xiaogang ZHANG ; Li CAO
Chinese Journal of Orthopaedics 2023;43(11):768-774
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.
5.Diagnostic value of plasma fibrinogen in chronic periprosthetic infection
Shuaifei TIAN ; Xiaobin GUO ; Yicheng LI ; Yushan NUERAIJIANG· ; Wulamu WUHUZI· ; Xiaogang ZHANG ; Li CAO
Chinese Journal of Orthopaedics 2023;43(13):891-897
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.
6.Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment.
Hao TIAN ; Juanfeng OU ; Yong WANG ; Jia SUN ; Junbin GAO ; Yicheng YE ; Ruotian ZHANG ; Bin CHEN ; Fei WANG ; Weichang HUANG ; Huaan LI ; Lu LIU ; Chuxiao SHAO ; Zhili XU ; Fei PENG ; Yingfeng TU
Acta Pharmaceutica Sinica B 2023;13(9):3862-3875
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.
7.Values of combined detection of indexes related to serum inflammation and platelet in diagnosis of chronic periprosthetic joint infection
Shuaifei TIAN ; Xiaobin GUO ; Yicheng LI ; Xiaogang ZHANG ; Li CAO
Chinese Journal of Orthopaedic Trauma 2022;24(9):786-792
Objective:To investigate the values of combined detection of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PC), platelet count/mean platelet volume (PC/MPV) and platelet plateletcrit (PCT) in the diagnosis of chronic periprosthetic joint infection (PJI).Methods:From January 2013 to December 2019, 441 patients underwent hip or knee joint revision at Department of Articular Surgery, The First Hospital Affiliated to Xinjiang Medical University. The patients were divided into a chronic PJI group and an aseptic prosthetic loosening group. In the chronic PJI group of 147 cases (86 hip ones and 61 knee ones), there were 64 males and 83 females, with a mean age of 66 (54, 72) years. In the aseptic prosthetic loosening group of 294 cases (210 hip ones and 84 knee ones), there were 98 males and 196 females, with a mean age of 63 (49, 72) years. The preoperative levels of CRP, ESR, PC, PC/MPV and PCT were compared between the 2 groups. The best cut-off value, sensitivity and specificity of the above indicators for the diagnosis of chronic PJI were recorded. The diagnostic efficacy of the 5 indicators in combination for chronic PJI was evaluated by comparing the area under the curve (AUC) among the indicators and analyzing the results of combined diagnostic detections.Results:Except for gender and joint revision site, there was no significant difference in the other general data between the 2 groups, showing comparability ( P>0.05). The levels of CRP, ESR, PC, PC/MPV and PCT in the PJI group were significantly higher than those in the aseptic prosthetic loosening group ( P<0.05). For CRP, ESR, PC, PC/MPV and PCT, respectively, the best cut-off values were 9.05 mg/L, 38.5 mm/h, 288×10 9/L, 29.34 and 0.33%, the sensitivities 83%, 71%, 44%, 44% and 33%, the specificities 85%, 86%, 84%, 84% and 90%, and the AUCs 0.868, 0.822, 0.688, 0.696 and 0.659. For CRP+ESR+PC+PC/MPV+PCT and CRP+PC+PC/MPV+PCT, respectively, the AUCs were 0.871 and 0.882, the sensitivities 80% and 84%, and the specificities 86% and 84%, showing significant differences in the diagnosis of chronic PJI compared with ESR, PC, PC/MPV and PCT alone ( P<0.05). Conclusion:In the diagnosis of chronic PJI, serum CRP and ESR combined with PC, PC/MPV and PCT have a reference value, but PC, PC/MPV or PCT alone only has a limited value.
8.Effects of acitretin on the level of interleukin-8(IL-8)in the peripheral blood of patients with pustular psoriasis
Jing TIAN ; Yicheng ZHOU ; Shuyun ZHENG ; Limei SUN ; Xin XIE
Chinese Journal of Dermatology 2011;44(10):732-734
Objective To investigate the changes of IL-8 in peripheral blood of patients with pustular psoriasis after acitretin treatment.Methods Dual antibody sandwich enzyme-linked immunosorbent assay (ELISA)was performed to measure the IL-8 levels in the peripheral blood of 30 patients with pustular psoriasis and 30 patients with psoriasis vulgaris before and after treatment,and in 30 normal human controls.The relationship between the IL-8 level and disease severity was assessed for patients with pustular psoriasis.Results After acitretin treatment,the condition was improved greatly in patients with pustular psoriasis,together with a significant decrease in the level of IL-8 in the peripheral blood(57.07 ± 12.02 pg/ml vs.96.84 ± 14.68 pg/ml,P < 0.05).Conclusion IL-8 may be involved in the therapeutic mechanism of acitretin in pustular psoriasis.
9.Expression of granulocyte macrophage-colony stimulating factor in patients with psoriasis
Xin XIE ; Li CHAI ; Yicheng ZHOU ; Na AN ; Jing TIAN
Chinese Journal of Dermatology 2011;44(10):731-732
Objective To investigate the expression of granulocyte macrophage-colony stimulating factor(GM-CSF)in skin lesions and sera of patients with pustular psoriasis and psoriasis vulgaris.Methods Tissue specimens were obtained from the lesions of 15 patients with pustular psoriasis,15 patients with psoriasis vulgaris and 15 normal human controls.Immunohistochemistry and dual antibody sandwich enzyme-linked immunosorbent assay(ELISA)were carried out to detect the levels of GM-CSF in the tissue and serum specimens from the patients and normal human controls,respectively.Results Significantly higher levels of GM-CSF were observed in the tissue and serum specimens from patients with pustular psoriasis and psoriasis vulgaris compared with the normal controls(all P < 0.01),as well as in those from the patients with pustular psoriasis compared with the patients with psoriasis vulgaris(both P < 0.01).Conclusion GM-CSF may be involved in the pathogenesis of psoriasis.
10.The application of PBL teaching method in dermatology and venereology
Limei SUN ; Jing TIAN ; Yicheng ZHOU
Chinese Journal of Medical Education Research 2002;0(01):-
To explore the application of Problem-Based Learning( PBL) method in the clinical teaching of dermatology,we discuss the specificity in teaching and problems in application of dermatology and venereology from the relations between dermatology and venereology and other subjects,between summary and each chapters,and the relationships between each diseases.

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