ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective:To evaluate the short-term efficacy and safety of 3D printing patient-matched artificial vertebral body in clinical research and application.Methods:A total of 12 patients with spinal tumors were enrolled 7 males (58.33%) and 5 females (41.67%), aged from 18 to 65 years old in The First Affiliated Hospital of Air Force military Medical University (hereinafter referred to as Xijing Hospital) and Peking University people's Hospital from September 2021 to July 2022. The spinal vertebra defect were restored by using 3D printing patient-matched artificial vertebral body after tumor resection. All patients who accepted TES and 3D printing patient-matched artificial vertebral body implantation were included according to the inclusion and exclusion criteria. The bone interface fusion was evaluated by the imaging fusion criteria of Brantigan and Steffee at 3 and 6 months after operation, the curative effect was evaluated by comparing Japanese Orthopaedic Association (JOA) score at 3 and 6 months after operation, visual analogue scale (VAS) 3 months after operation and intervertebral height at 3 and 6 months after operation with those before operation, and the safety was evaluated by adverse event recording.Results:All 12 patients completed the operation successfully, and the operation sites were thoracic vertebrae in 6 cases (50%), thoracolumbar in 3 cases (25%) and lumbar vertebrae in 3 cases (25%). All patients were followed up. The mean follow-up time was 23.92±3.23 months (range, 19-29 months). No tumor recurrence or metastasis was observed during this period. All patients were followed up at 15 days, 3 months and 6 months after operation. During the 6-month follow-up, X ray results showed that interface of bone and the vertebral body were fused in all of the 12 patients, and the effective rate of fusion was 100%. The 95% confidence interval is calculated to be (75.6%-100%). Six months after operation, the improvement rate of JOA score was excellent in 10 cases, good in 1 case, poor in 1 case, and the excellent and good rate was 91.66%. The preoperative VAS score was 4.08 ±2.47, and during the 3-month follow-up, the VAS score was improved to 1.83 ±1.59. Compared with the preoperative VAS score, the difference was statistically significant ( t=2.635, P=0.023). The intervertebral height before operation, 15 days after operation, 3 months after operation and 6 months after operation were 32.75 (25.94, 68.20), 41.09 (30.55, 70.20), 40.70 (30.23, 67.83) and 40.74 (30.23, 67.08), respectively, and there was no statistically significant difference (χ 2=0.768, P=0.857). No implant-related adverse events occurred after operation. Conclusion:The 3D printing patient-matched artificial vertebral body used in this study has satisfactory short-term efficacy and safety in the reconstruction of spinal stability after spinal tumor resection.

The tendon-bone interface is where the tendons or ligaments are connected with the bones. A spectrum of injuries may happen to the "soft-to-hard" tissue interface, including those to the rotator cuff-bone and cruciate ligament-bone interfaces, which are often precipitated by a combination of degenerative changes on the tendon-bone interface and acute or chronic injuries, thus severely impairing the patients′ motor function. In recent years, with the deepening of the interdisciplinary researches in biomechanics, mechanobiology, and sports medicine, the role of mechanical factors in the repair of tendon-bone interface injuries has attracted more and more attention and becomes a focus of the edge-cutting researches on the tendon-bone interface injuries. To this end, the authors proposed the concept of "tendon-bone interface mechanomedicine" based on an overview of the relevant researches at home and abroad. The mechanical properties of the tendon-bone interface and the effects of mechanical stimuli on its biological behavior were elucidated from the four aspects: biomechanics, mechanobiology, mechanodiagnostics, and mechanotherapy, aiming to explore the diagnostic and therapeutic strategies for tendon-bone interface injuries from the angle of mechanics and provide new perspectives and methodologies for the field of tendon-bone interface injury repair.

Objective:To construct a diabetic foot classification prediction model based on radiomics features of fundus photographs.Methods:A total of 2 035 fundus photographs of patients with type 2 diabetes diagnosed at Nanfang Hospital between December 2011 and December 2018 were retrospectively collected [282 photographs from patients with diabetic foot(DF), and 1 753 from patients with diabetes mellitus(DM)]. All fundus photographs were randomly divided into a training set(1 424 photos) and a test set(611 photos) using a computer generated random number at 7∶3. After pre-processing the fundus photographs, a total of 4 128 texture features based on the gray matrix were extracted by the Radiomic toolkit, and 11 339 other features were extracted using the ToolboxDESC toolkit. The LASSO algorithm was used to select the 30 features most relevant to DF, and then the Bootstrap + 0.632 self-sampling method was used to further select the 7 best combinations. Logistic regression analysis was used to obtain the regression coefficients and establish the final diabetic foot classification prediction model. ROC curve was drawn, and AUC, sensitivity, specificity, and accuracy of the training and test sets were calculated to verify its prediction performance. Results:We screened 7 fundus radiomics markers for diabetic foot patients, and based on this established a DF/DM classification prediction model. The AUC, sensitivity, specificity, and accuracy of the model were 0.958 6, 0.984 0, 0.920 0, and 0.928 0 in the training set, and 0.927 1, 0.988 9, 0.881 0, and 0.896 9 in the test set, respectively.Conclusion:In this study, seven DF fundus markers were screened using radiomics technology. Based on this, a highly accurate and easy-to-use DF/DM classification model was constructed. This technology has the potential to increase the efficiency of DF screening programs.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Objective:The residual cancer burden (RCB) evaluation system was used to analyze the influencing factors of the efficacy of neoadjuvant therapy in breast cancer, and to explore the prognostic value of RCB evaluation in neoadjuvant therapy.Methods:Clinicopathologic data and postoperative RCB grading of 364 breast cancer patients who underwent neoadjuvant therapy in Renmin Hospital of Wuhan University from Nov. 2019 to Nov. 2022 were collected. Chi-square test was used to analyze the relationship between RCB grading and clinicopathological parameters, and Spearman’s rank correlation analysis was performed to evaluate the correlation between RCB grading and clinicopathological characteristics. Factors influencing pathologic complete response (pCR) were analyzed by Logistic regression. Kaplan-Meier survival analysis and log-rank test were used to evaluate cumulative survival.Results:Among the 364 patients who underwent neoadjuvant therapy, 129 cases of RCB grade 0 and 235 cases of RCB gradeⅠ-Ⅲ (including 46 cases of RCB gradeⅠ, 109 cases of RCB grade Ⅱ and 80 cases of RCB grade Ⅲ) were obtained after surgery. Histological classification ( χ 2=21.757, P=0.000), estrogen receptor (ER) ( χ 2=52.837, P=0.000), progesterone receptor (PR) ( χ 2=55.658, P=0.000), human epidermal growth factor receptor-2 (HER2) ( χ2=89.040, P=0.000), Ki67 expression ( χ2=12.927, P=0.005), molecular typing ( χ 2=80.793, P=0.000) and preoperative lymph node status ( χ 2=25.764, P=0.000) were all associated with postoperative RCB grading. Further correlation analysis showed that histological grade ( r=-0.229, P=0.000), HER2 expression ( r=-0.465, P=0.000) and Ki67 expression ( r=-0.179, P=0.000) were negatively correlated with RCB grading, while ER ( r=0.352, P=0.000), PR ( r=0.379, P=0.000) and lymph node metastasis ( r=0.214, P=0.000) were positively correlated with RCB grading. Logistic regression analysis showed that high histological grade, negative expression of ER, PR and AR, positive expression of HER2, high proliferation index of Ki67 and no lymph node metastasis were favorable factors for postoperative pCR, and PR, AR and HER2 were independent predictors of postoperative pCR. Kaplan-Meier survival analysis showed significant differences in postoperative cumulative survival among patients with different RCB grades ( P=0.004) . Conclusions:Postoperative RCB grading of breast cancer is closely related to many clinicopathological features before neoadjuvant therapy and survival prognosis. Clinicopathological factors closely related to RCB grading are also important influencing factors affecting the pCR of patients with neoadjuvant therapy. Therefors, RCB grading has a high prognostic value.

Objective To establish a project team to assess and manage the risk of out-of-town transport of extracorporeal membrane oxygenation(ECMO)patients using the healthcare failure mode and effects analysis(HFMEA),analyze the effectiveness of its application,and develop targeted improvement measures and processes.Methods Patients with ECMO who were treated in the department of intensive care unit(ICU)of Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine March 2020 to September 2021 were selected as the study subjects.By comparing the differences in the accuracy of ECMO transport risk assessment,the rate of fixation against catheter slippage,the incidence of adverse transport events between the two groups before and after HFMEA,and the application effect of this model in ECMO transport adverse event risk management was evaluated.Results A total of 48 ECMO patients were enrolled,and 42 times of out-of-home transfers were performed,including 22 before HFMEA and 20 after HFMEA.Compared with pre-HFMEA,the accuracy of ECMO transport risk assessment[95.00%(19/20)vs.54.55%(12/22),P＜0.05]and the compliance rate of catheter slip fixation[100.00%(20/20)vs.68.18%(15/22),P＜0.05]in patients after HFMEA were significantly increased,the incidence of adverse events in transport was significantly lower[5.00%(1/20)vs.40.91%(9/22),P＜0.05].Conclusion The application of HFMEA in the risk management of ECMO transshipment adverse events is beneficial to standardize the prevention of ECMO transshipment accidents,effectively reduce the incidence of transshipment adverse events,and ensure patient safety.

Objective    To analyze the occurrence of postoperative pulmonary complications (PPC) and the risk factors in patients with spontaneous pneumothorax who underwent micro single-port video-assisted thoracoscopic surgery (VATS). Methods    A total of 158 patients with spontaneous pneumothorax who underwent micro single-port VATS in our hospital from April 2017 to December 2019 were retrospectively included, including 99 males and 59 females, with an average age of 40.53±9.97 years. The patients were divided into a PPC group (n=21) and a non-PPC group (n=137) according to whether PPC occurred after the operation, and the risk factors for the occurrence of PPC were analyzed. Results    All 158 patients successfully completed the micro single-port VATS, and there was no intraoperative death. The postoperative chest tightness, chest pain, and dyspnea symptoms basically disappeared. During the postoperative period, there were 3 patients of pulmonary infection, 7 patients of atelectasis, 4 patients of pulmonary leak, 6 patients of pleural effusion, 1 patient of atelectasis and pleural effusion, and the incidence of PPC was 13.29% (21/158). Multivariate logistic regression analysis showed that lung disease [OR=32.404, 95%CI (2.717, 386.452), P=0.006], preoperative albumin level≤35 g/L [OR=14.912, 95%CI (1.719, 129.353), P=0.014], severe pleural adhesions [OR=26.023, 95%CI (3.294, 205.557), P=0.002], pain grade Ⅱ-Ⅲ 24 hours after the surgery [OR=64.024, 95%CI (3.606, 1 136.677), P=0.005] , age [OR=1.195, 95%CI (1.065, 1.342), P=0.002], intraoperative blood loss [OR=1.087, 95%CI (1.018, 1.162), P=0.013] were the risk factors for PPC after micro single-port VATS. Conclusion    There is a close relationship between PPC after micro single-port VATS and perioperative indexes in patients with spontaneous pneumothorax. Clinically, targeted prevention and treatment can be implemented according to the age, pulmonary disease, preoperative albumin level, intraoperative blood loss, degree of pleural adhesion and pain grading 24 hours after surgery.

Objective:To explore the influencing factors of lower extremity ischemic injury in patients with extracorporeal membrane oxygenation (ECMO) .Methods:From July 2016 to December 2020, convenience sampling was used to select 123 ECMO patients admitted to the Intensive Care Unit, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine as the research object. Based on the occurrence of lower extremity ischemia, the patients with lower extremity ischemia were included in the ischemic injury group ( n=21) , and the patients without lower extremity ischemia were included in the non-ischemic injury group ( n=102) . The clinical data of the two groups of patients were collected, and the influencing factors of lower extremity ischemia in ECMO patients were analyzed by multivariate Logistic regression. Results:Multivariate Logistic regression analysis showed that diabetes, cardiac arrest, left ventricular ejection fraction, and ECMO adjuvant time were all influencing factors for lower extremity ischemia in ECMO patients, and the differences were statistically significant ( P<0.05) . Conclusions:The occurrence of lower extremity ischemia in ECMO patients is related to factors such as diabetes mellitus and left ventricular ejection fraction, which needs medical and nursing staff to attach great importance to it and take measures to actively prevent it.