OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

Cannabinoid type 1 receptor(CB1R)is one of the most widely studied endocannabinoid receptors in recent years,which is expressed in both central and peripheral nerve systems.CBIR is located in the presynaptic membrane,and regulates the release of neurotransmitters through retrograde inhibitory synaptic transmission,which is an effective target for the treatment of pain.Activation of CB1R has analgesic effect on injurious,pathological,and inflammatory pain,and antagonism of CB1R can cause pain sensitization.This article describes CB1R from the aspects of structure and function,signal transduction,and analgesic mechanism,so as to provide reference for further understanding the pathophysiology of pain and exploring better pain treatment methods.

Objective To address the problem of late strut thrombosis generated after the implantation of biodegradable vascular stents,a stochastic finite element model was established to perform biomechanical analysis on the degradation process of polymer vascular stent from the perspectives of molecular weight and stress.Methods A mathematical model of the degradation process of biodegradable vascular scaffolds using poly lactic acid(PLA)was established and the mathematical model was imported,and a finite element model was constructed using COMSOL software.The model was stochastically used to analyze the effects on molecular weight and stress distribution in the degradation process under different stochastic parameters and standard deviations.Results During the degradation process of degradable polymer vascular scaffolds in human body,the random variables Mn0 and 8%standard deviation had the most significant effects on the distribution of molecular weights;randomization of the parameters led to a wider distribution range of the fracture strength during the degradation process of polymer vascular scaffolds,and the minimum value of fracture strength was lower.Conclusions The inhomogeneity of molecular weight distribution in polymer vascular stent materials leads to differences in mechanical properties at different locations of the stent,which in turn causes stress concentration within the material,ultimately leading to non-uniform fragmentation of the stent during degradation,which becomes a determining factor for stent thrombosis in later stages.This study provides theoretical guidance for designing next-generation biodegradable vascular stents.

Objective To explore the teaching effect of case-integrated scenario simulation instruction model on proba-tionary instruction of acute upper gastrointestinal bleeding.Methods A total of 40 medical students of grade 2021 majoring in clinical medicine,namely,Nanshan Class,from Guangzhou Medical University were selected as participants.The students were randomly divided into two groups,with 22 as an experimental group and 18 as a control group.The former group received the case-integrated based scenario simulation teaching model,while the latter adopted the traditional bedside teaching model.The teaching content was on acute non-variceal upper gastrointestinal bleeding.Results There was no statistically significant differ-ence in the total score of gastroenterology between the experimental group and the control group(P＞0.05).The experimental group scored significantly higher in the gastrointestinal bleeding-related contents compared to the control group(P＜0.05).The post-class survey revealed that the majority of the students in the research group expressed their high-level satisfaction with the new instruction model and demonstrated their greater interests in participation in the new instruction model.Conclusion The case-integrated scenario simulation instruction model demonstrates significant superiority to the traditional bedside teaching model in terms of stimulating learning interests,cultivating medical professionalism,and enlivening classroom atmosphere.It is suitable for practical teaching in gastroenterology and can be widely adopted as routine probationary teaching for undergraduate students.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective:To compare the difference between virtual surgical planning(VSP)position and postoperative real position of maxilla and condyle,and to explore the degree of intraoperative realization of VSP after orthognathic surgery.Methods:In this study,36 patients with mandibular protrusion de-formity from January 2022 to December 2022 were included.All the patients had been done bilateral sagittal split ramus osteotomy(SSRO)combined with Le Fort Ⅰ osteotomy under guidance of VSP.The VSP data(T0)and 1-week postoperative CT(T1)were collected,the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software.At the same time,accor-ding to the morphology of palatal folds,the virtual design was registered with the postoperative model,and the unclear maxillary dentition in the postoperative model was replaced.Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the opera-tion.The three-dimensional reference plane and coordinate system were established.Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement,we compared the coordinate changes of marker points in three directions,and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP.Results:The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions,and the anteropos-terior deviation was about 1.5 mm.In addition,most patients had a certain degree of counterclockwise rotation of the maxilla after surgery.Most of the bilateral condyle moved forward,outward and downward(the average distance deviation was 0.15 mm,1.54 mm,2.19 mm,respectively),and rotated forward,outward and upward(the average degree deviation was 4.32°,1.02°,0.86°,respectively)compared with the VSP.Conclusion:VSP can be mostly achieved by assistance of 3D printed occlusal plates,but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP,which may be related to the rotation axis of the mandible in the VSP.It is necessary to use patient personalized condylar rotation axis for VSP,and apply condylar positioning device to further improve surgical accuracy.

Portal vein thrombosis （PVT） is one of the common complications during the natural course of liver cirrhosis and has an important influence on the progression of liver cirrhosis. This article mainly summarizes the research advances in the risk factors for PVT. There are many risk factors for PVT， and Virchow’s triad， namely venous stasis， hypercoagulability， and vascular endothelial injury and systemic inflammation caused by surgery or trauma， are considered the main reasons for the development and progression of PVT. At present， more prospective studies are still needed to validate the predictive models for the risk of PVT that have certain application prospects in clinical practice. Cirrhotic patients with PVT tend to have a poor prognosis， and complete obstructive PVT is associated with increased mortality after liver transplantation. Recent studies have shown that prophylactic anticoagulant therapy is safe and effective in patients with liver cirrhosis and can thus help with the prevention and treatment of PVT.

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

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].