1.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
2.Mechanisms of Qizhujianwei Granules in Blocking Malignant Progression of Gastric Intraepithelial Neoplasia
Yuling YU ; Yanmin WANG ; Siqi WANG ; Yateng SUN ; Yunhe WANG ; Yonghuang YAN ; Xinyu YANG ; Siqi HAN ; Yuhong SONG ; Yuhan WANG ; Cai ZHANG ; Zeqi SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):143-151
ObjectiveTo investigate the effects of Qizhujianwei granules (QZJW) on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia (GIN) and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine (MNNG), ranitidine, irregular feeding patterns, and sodium salicylate. Except for the normal group, after successful modeling, the rats were randomly divided according to body weight into a model group, a Moluodan group (0.55 g·kg-1), and a QZJW group (7.34 g·kg-1), with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pepsinogenⅠ (PGⅠ), pepsinogenⅡ (PGⅡ), and gastrin (G-17), as well as the expression level of transforming growth factor-β1 (TGF-β1) in gastric mucosal tissue, and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry (IHC) was used to detect the localization and expression levels of proliferating cell nuclear antigen (Ki-67) and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A (Wnt3a), β-catenin, CyclinD1, proto-oncogene Cmyc, transforming growth factor-β receptor Ⅰ (TGFβRⅠ), intracellular signaling transducers Smad2/3, phosphorylated (p)-Smad2/3, twist family transcription factor (Twist1), and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group, the model group showed characteristic changes including dim eyes, pale ears and claws, dark-red tongue, and reduced luster of the tail. The gastric mucosa appeared pale, with surface congestion and erosion. The gastric mucosal glands were disordered, the nuclear-to-cytoplasmic ratio increased, and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased (P<0.01), while the level of G-17 was significantly increased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly increased (P<0.05, P<0.01), whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased (P<0.05). Compared with the model group, the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased (P<0.05, P<0.01), while the level of G-17 was significantly decreased (P<0.01). The protein expression levels of Ki-67, Wnt3a, β-catenin, CyclinD1, Cmyc, TGF-β1, TGFβRⅠ, Smad2/3, Twist1, and Vimentin in gastric mucosal tissue were significantly decreased (P<0.05, P<0.01). ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile, it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β1/Smad/Twist1 signaling pathway, thereby blocking the malignant progression of GIN.
3.Mechanism of Zuogui Wan in Improving Nephrotic Syndrome in Rats Based on Regulating Gut Microbiota
Xinyu HU ; Tubei ZHANG ; Yixin HU ; Rui WANG ; Zhili XIONG ; Yan CAI ; Xuerong ZHANG ; Linqun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):32-41
ObjectiveTo investigate the protective effects of Zuogui Wan (ZGW) decoction on nephrotic syndrome (NS) through the regulation of gut microbiota. MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into five groups, with 6 rats in each group: The control group, model group, low-dose group, medium-dose group, and high-dose group. The NS rat model was induced by tail vein injection of 6.5 mg·kg-1 doxorubicin. After successful modeling, the control and model groups were gavaged with normal saline (10 mL·kg-1) twice daily, while the low- (50 mg·kg-1), medium- (100 mg·kg-1), and high-dose (200 mg·kg-1) groups were gavaged with ZGW (10 mL·kg-1) twice daily. All rats were administered at fixed intervals daily for 8 consecutive weeks. The therapeutic effects of ZGW on NS in rats were observed, and the optimal dose was screened. Renal and intestinal pathological changes in rats were examined. Fecal samples were collected, and 16S rDNA sequencing technology was used to detect the diversity and abundance of gut microbiota in each group. ResultsCompared with the control group, 24-hour urinary protein, serum creatinine, urea nitrogen, and cholesterol levels significantly increased in the model group (P<0.01), while serum albumin levels decreased (P<0.01). These changes were ameliorated in the treatment groups (P<0.05, P<0.01). Renal pathology revealed intact and orderly arranged glomeruli and renal tubules in the control group. In the model group, glomerular atrophy, widened mesangial areas, podocyte swelling, disordered renal tubular arrangement, and numerous casts were observed. Varying degrees of glomerular atrophy and disordered renal tubular arrangement were seen in the treatment groups. Specific protein assays revealed increased serum levels of kidney injury molecule-1(KIM-1) and α1-microglobulin (P<0.01), and significantly decreased levels of E-cadherin, Podocin, and Nephrin in renal tissues (P<0.01), along with a significant increase in transforming growth factor-β(TGF-β) (P<0.01) in the model group. In the treatment groups, serum KIM-1 and α1-microglobulin levels decreased, E-cadherin levels significantly increased (P<0.01), and TGF-β levels significantly decreased (P<0.01). Podocin and Nephrin levels increased in the high-dose group (P<0.05). Additionally, intestinal mucosal atrophy, epithelial cell edema, decreased goblet cells, and multiple inflammatory infiltrations were observed in the model group. The sequencing results of gut microbiota demonstrate that ZGW can significantly ameliorate intestinal dysbiosis in rats, restore the abundance of beneficial bacteria, and exert a profound influence on the compositional profile of gut microbiota. ConclusionZGW can alleviate renal injury in rats with nephrotic syndrome by improving gut microbiota and protecting the intestinal barrier.
4.Analysis of Current Status and Prospects of Traditional Chinese Medicine in Responding to Public Health Emergencies Under Healthy China Strategy: Taking Major Emerging Epidemics as an Example
Yuqing CAO ; Xinyu JI ; Xiyu SHANG ; Qiujie CAI ; Yipin FAN ; Yanping WANG ; Yan MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):222-232
Under the background of the Healthy China strategy, the integration of traditional Chinese medicine (TCM) into the public health emergency response system has become an important measure to enhance the capacity for coping with public health emergencies. In recent years, the role of TCM in responding to such emergencies has become increasingly prominent. Taking major emerging epidemics as an example, TCM has developed a rich theoretical system and practical experience in epidemic prevention and treatment over thousands of years, and has played a significant role in successive outbreaks with its unique advantages. Based on the concept of ''preventing disease before its onset'' and the theoretical framework of treatment based on syndrome differentiation, TCM has achieved remarkable results through early intervention and full participation in the integrated model of TCM and Western medicine, from severe acute respiratory syndrome (SARS) to corona virus disease-2019 (COVID-19), in improving clinical symptoms and outcomes, reducing adverse reactions, and promoting recovery. From the perspective of the Healthy China strategy, this paper systematically reviews the historical development of TCM in epidemic prevention and treatment, with particular attention to recent epidemics such as SARS, influenza A (H1N1), and COVID-19. It further examines the similarities and differences between TCM and Western medicine in responding to major emerging epidemics, as well as relevant policies related to TCM in epidemic prevention and control. In addition, it summarizes the existing problems in TCM's role in the prevention and treatment of major emerging epidemics, and explores measures to improve its rapid response capacity under the Healthy China strategy. This study not only provides a ''Chinese solution'' for the prevention and control of newly emerging infectious diseases worldwide, but also offers theoretical and practical references for strengthening the public health emergency response system, carrying strategic significance for promoting the modernization and internationalization of TCM.
5.Diagnosis and treatment of colorectal liver metastases: Chinese expert consensus-based multidisciplinary team (2024 edition).
Wen ZHANG ; Xinyu BI ; Yongkun SUN ; Yuan TANG ; Haizhen LU ; Jun JIANG ; Haitao ZHOU ; Yue HAN ; Min YANG ; Xiao CHEN ; Zhen HUANG ; Weihua LI ; Zhiyu LI ; Yufei LU ; Kun WANG ; Xiaobo YANG ; Jianguo ZHOU ; Wenyu ZHANG ; Muxing LI ; Yefan ZHANG ; Jianjun ZHAO ; Aiping ZHOU ; Jianqiang CAI
Chinese Medical Journal 2025;138(15):1765-1768
6.Influencing factors for medication adherence among inpatients with chronic diseases based on latent profile analysis
WANG Xiaoshan ; YE Lixiang ; CHEN Li ; LI Minxiang ; WANG Xinyu ; CAI Xiaoxia
Journal of Preventive Medicine 2025;37(3):217-222
Objective:
To explore the types of medication adherence and their influencing factors among inpatients with chronic diseases based on latent profile analysis, so as to provide the basis for improving medication adherence among patients with chronic diseases.
Methods:
The inpatients with chronic diseases admitted to the Second Affiliated Hospital of Hainan Medical University were selected as the study subjects. Demographic information, chronic disease status, and health education were collected through questionnaire surveys. Medication adherence was assessed using the Medication Adherence Scale and categorized based on the scores of its eight items through latent profile analysis. Factors affecting medication adherence among inpatients with chronic diseases were analyzed using a multinomial logistic regression model.
Results:
Totally 290 valid questionnaires were recovered, with an effective recovery rate of 97.64%. There were 157 males (54.14%) and 133 females (45.86%), with a median age of 61 (interquartile range, 21) years. The median score of medication adherence was 4.75 (interquartile range, 4.50). Based on latent profile analysis, medication adherence was categorized into three types: subjective neglect with poor adherence (38.97%), subjective confidence with fluctuating adherence (28.28%), and self-reflective with good adherence (32.76%). Multinomial logistic regression analysis showed that compared to the subjective confidence with fluctuating adherence, family monthly income (5 000-10 000 yuan, OR=2.981, 95%CI: 1.055-8.429), comorbidity of chronic diseases (OR=3.478, 95%CI: 1.579-7.661), number of health education sessions received in the past year (≤1 session, OR=0.329, 95%CI: 0.120-0.907; 2 sessions, OR=0.363, 95%CI: 0.138-0.950), and health information literacy scores (<60 points, OR=2.596, 95%CI: 1.209-5.573) were statistically associated with subjective neglect with poor adherence (all P<0.05).
Conclusion
Subjective neglect with poor medication adherence among inpatients with chronic diseases is associated with family monthly income, comorbidity of chronic diseases, the number of health education sessions received, and health information literacy.
7.Effectiveness of three-dimensional-printed microporous titanium prostheses combined with flap implantation in treatment of large segmental infectious bone defects in limbs.
Yongqing XU ; Xinyu FAN ; Teng WANG ; Shaoquan PU ; Xingbo CAI ; Xiangwen SHI ; Wei LIN ; Xi YANG ; Jian LI ; Min LIU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):521-528
OBJECTIVE:
To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs.
METHODS:
A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score.
RESULTS:
All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76).
CONCLUSION
The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans
;
Male
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Female
;
Middle Aged
;
Printing, Three-Dimensional
;
Titanium
;
Retrospective Studies
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Surgical Flaps
;
Adult
;
Prosthesis Implantation/methods*
;
Plastic Surgery Procedures/methods*
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Treatment Outcome
;
Prostheses and Implants
;
Bone Diseases, Infectious/surgery*
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Extremities/surgery*
;
Prosthesis Design
8.Clinical features and prognosis of acute B lymphoblastic leukemia children carrying a TCF3: : PBX1 fusion gene
Lulu HUANG ; Yunyan HE ; Yang LI ; Danna LIN ; Ning LIAO ; Yayun LING ; Lyuhong XU ; Xinyu LI ; Huirong MAI ; Ying WANG ; Wuqing WAN ; Ying LIU ; Yanlai TANG ; Xiaoli ZHANG ; Chuan TIAN ; Xiaofeng LI ; Qiwen CHEN ; Xingjiang LONG ; Liuhua LIAO ; Qiaoru LI ; Jianling CAI ; Zijun ZHEN ; Zhiguang LI ; Keyan YANG ; Qinlong ZHENG ; Lihua YANG
Chinese Journal of Applied Clinical Pediatrics 2025;40(7):497-502
Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.
9.Short-term efficacy of a 3D printed microporous titanium prosthesis in the treatment of large segmental tibial defects
Yongqing XU ; Xinyu FAN ; Teng WANG ; Shaoquan PU ; Xingbo CAI ; Wei LIN ; Xi YANG ; Xia LI ; Jian SHI ; Yipeng WU ; Jian LI ; Min LIU
Chinese Journal of Orthopaedic Trauma 2025;27(6):529-535
Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.
10.Celecoxib improves right heart function in mice after acute high-altitude hypoxia exposure by increasing 12,13-diHOME level
Wei ZHANG ; Xinyu BAO ; Xiaoyue LAI ; Xiaoqin WAN ; Yan TAN ; Hongjun YIN ; Xiaoshi CAI ; Dingyuan TIAN ; Ziyang WANG ; Pan ZHENG ; Fang DENG ; Zhihui ZHANG
Journal of Army Medical University 2025;47(19):2289-2301
Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.


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