Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals ; Zebrafish ; Hair Cells, Auditory/physiology* ; Lateral Line System/cytology* ; Escape Reaction/physiology* ; Larva ; Mice ; Cisplatin/toxicity* ; Drug Evaluation, Preclinical/methods*

Diabetic gastroparesis （DGP） is a common diabetic neuropathy that affects the normal function of gastric motility and emptying. Clinically， it often manifests as abdominal distension， nausea and vomiting， early satiety， dyspepsia， etc. The pathogenesis of DGP is multifactorial， closely related to many factors， such as chronic hyperglycemia， neuropathy， autonomic nervous system disorders， inflammation， and oxidative stress. These factors can interact with each other， leading to delayed gastric emptying and the occurrence of related symptoms. Traditional Chinese medicine （TCM） has significant advantages in the prevention and treatment of DGP， including a long history， remarkable efficacy， individualized treatment， diverse therapeutic formulations， and improvement in the quality of life. Additionally， TCM is known for its low adverse reactions， good tolerance， and multi-targeted effects， making it an important approach in the management of DGP. Previous research has found that the main mechanisms of Chinese medicine in the prevention and treatment of DGP include the regulation of gastrointestinal hormones， inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and modulation of related signaling pathways such as stem cell factor （SCF）/cellular growth factor receptor （c-Kit）， adenosine monophosphate-activated protein kinase （AMPK）， Ras homologous genome member A （RhoA）/Rho-associated coiled-coil forming kinase （ROCK）. This article primarily summarized the research progress on Chinese medicine in preventing and treating DGP through the inhibition of inflammatory responses， reduction of oxidative stress， enhancement of interstitial cells of Cajal activity， inhibition of pyroptosis， and regulation of related signaling pathways， aiming to provide a reference and basis for further research on the application value of Chinese medicine in the prevention and treatment of DGP.

OBJECTIVE To identify the influence factors associated with 28-day fatality among COVID-19 hospitalizations and to analyze the interaction between the disease severity at admission and the use of hospital preparations.METHODS A retrospective review of records from COVID-19 hospitalizations aged 18 to 90 who were admitted to the Jiangsu Province Hospital of Chinese Medi-cine from December 15,2022 to January 15,2023 were conducted.Patients who died or were lost to follow-up within 48 h of admis-sion were excluded.Patients were divided into survival and death groups based on their 28-day fatality status.Descriptive statistics were used to characterize the two groups and multivariate logistic regression models were employed to identify factors influencing 28-day fatality risk.The interaction between the severity of illness at admission and the use of hospital preparations was explored through cross-over analysis and hierarchical regression analysis.RESULTS Significant differences were observed between the survival and death groups in terms of severity of illness at admission,hospital preparations usage,steroid therapy,age,platelet count,lactate dehydro-genase levels,and urea(P<0.05.Crossover analysis and hierarchical logistic regression analysis revealed a significant antagonistic interaction between the severity of illness at admission and the use of hospital formulations both before adjustment(RERI=-20.678,95%CI:-33.703～-7.652;APAI=-2.301,95%CI:-4.027～-0.575 and after adjusting for gender,age,clinical characteristics and further adjusting for laboratory parameters(RERI=-5.972,95%CI:-10.564～-1.380;APAI=-2.205,95%CI:-4.131～-0.279,and it was an antagonistic interaction both before(SI=0.279,95%CI:0.157～0.493 and after adjustment(SI=0.222,95%CI:0.095～0.523.CONCLUSION The use of hospital preparations significantly reduces the 28-day fatality risk among COV-ID-19 hospitalizations and a clear antagonistic interaction was observed between the disease severity at admission and the use of hospi-tal preparations.

Objective To explore the possible role of thrombospondin-1(THBS1)in the excessive fibrosis of vaginal wall induced by estrogen deficiency in rats,the morphological structure of collagen fibers and the expression of THBS1 in the vaginal wall were detected in the estrogen deficiency model of rats.Methods Twenty-four SD rats aged 3 months without delivery were randomly divided into sham operation group and experimental group,with 12 rats in each group.After 12 weeks of modeling,the rats were killed and the vaginal walls were taken for analysis.Masson staining was used to observe the morphological and structural changes of collagen fibers in vaginal wall of rats.Immunohistochemical staining and Western blotting were used to detect the expression level of THBS1 protein.Results After 12 weeks of modeling,the uterine atrophy of experimental group was obvious,the increase of body mass was significantly higher than that of sham operation group,and the level of estradiol was significantly lower than that of sham operation group(P<0.01).Compared with the sham operation group,the upper cortex of vaginal wall of experimental group was significantly atrophy,the smooth muscle bundles were thinner,the muscle gap was wider,the collagen fiber deposition in lamina propria and muscle layer was increased,and the arrangement and distribution were disordered and fragmented.THBS1 expression in vaginal wall of experimental group was significantly higher than that of sham operation group(P<0.05).Conclusion Estrogen deficiency may mediate excessive fibrosis of vaginal wall by upregulating THBS1 expression,thereby damaging the biomechanical properties of vaginal wall and leading to an increased susceptibility to pelvic organ prolapse development.

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Objective: To assess plantar arch index (AI) and prevalence of flat feet in school-age children (7-12 years old) in Shanghai and evaluate the relationship between flat feet with age, gender, weight status (BMI) and occurring sides, and to provide a reference for the prevention of flatfeet. Methods: Three-dimensional foot measuring instruments were used to measure bilateral foot length, medial arch height, AI and arch height ratio (AHR) in school-age children in Shanghai. Statistical analysis of these foot parameters was performed. Results: A total of 3 226 children between aged 7 and 12 in Shanghai were measured with AI of (0.27±0.05) and AHR of (3.02±1.89). Prevalence of flat feet in the group of 7 to 12 year old children was 56.1%. Prevalence of flatfeet decreased significantly with age: 72.6% at 7 years old and 37.9% at 12 years old. Boys had a significantly greater risk for flat feet than girls: the prevalence of flat feet was 62.9% for boys and 47.8% for girls (OR=1.81, 95%CI=1.57-2.10). This risk was independent of age but related to gender. The risk of flat feet in boys was always higher than that in girls at every age. For children aged 7-8, being overweight was not significantly related to the occurrence of flat feet. However, for children aged 9-12 who were overweight were more likely to have flat feet than those of normal weight. The OR increased with age: from 1.44 (95%CI=1.03-2.03) at 9 to 2.96 (95%CI=1.68-5.23) at 12. There was no difference on which side flat feet would occur (χ2=0.95，P=0.33). Conclusion This finding shows that prevalence of flat feet is influenced by age, gender and weight status. AI and prevalence of flat feet in children aged 7-12 decreases with age, and boys have significantly higher prevalence of flat feet than girls. Overweight children aged 9 or older have a higher risk of flat feet.

Objective: To study the use of a three dimensional (3D) visualization operative planning system in Ultrasound-guided percutaneous microwave ablation (US-PMWA) for large hepatic hemangiomas (LHHs). Methods: A total of 50 patients with LHHs from January 2011 to August 2018 were included in Department of Interventional Ultrasound, the First Medical Center, Chinese PLA General Hospital, including 12 males and 38 females (age from 28.0~60.0, mean age was 43.0). Fifty patients with LHHs were divided into the 3D and 2D groups (25 cases in each group). The therapeutic efficacy was assessed by contrast-enhanced imagings on follow-up. Hepatic and renal functions were studied. The complete ablation, tumor volume shrinkage and complication rates were analyzed. Results: The levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and creatinine after ablation in the 3D group were significantly lower than the 2D group [(126.7±56.4)U/L vs. (204.7±76.5)U/L; (141.0±60.8)U/L vs. (206.6±77.4)U/L; (57.3±17.6)U/L vs. (86.2±46.1)U/L; (66.6±16.6)mmol/L vs. (86.8±42.8)mmol/L, P<0.05, respectively]. Compared with the 2D group, the ablation energy, ablation time and proportion of hemoglobinuria in the 3D group were all significantly less, while the complete ablation rate was significantly higher [(93.7±3.3)% vs. (97.7±2.4)%](all P<0.05). Conclusion The 3D visualization operative planning system provided a scientific, quantifiable, and individualized therapy for LHHs using US-PMWA.

Objective: To identify the optimal placement of bone tunnel during near-isometric anterior cruciate ligament reconstruction (ACLR), and its dimensional relationship with knee anatomic structure after summarizing published researches. Methods: PubMed, Embase, and CNKI were screened for Chinese or English articles on clinical studies, cadaveric studies of knee and reviews on bone tunnel placement in anterior cruciate ligament near-isometric reconstruction and isometry of native anatomic fibers. Related articles were extracted and systematically reviewed. Results: A total of 21 articles were finally included after screening. This systematic review found that most of the literatures were cadaveric studies, among which three dimensional imaging techniques, combined with cadaveric studies, were commonly used as a method of determining the length change between spots on the tibial plateau and lateral condyle of femur in recent years. There were 3 case series and 1 prospective cohort study. On the side of lateral condyle of femur, Blumensaat's line, lateral intercondylar ridge and insertion of intact anterior cruciate ligament were commonly used as reference to describe the near isometric area, while on the side of tibial plateau, the anterior horn of lateral meniscus were used as reference for reconstruction. The bone tunnel on tibial side was ignored compared with the femoral side when considering the isometry of reconstruction. There were overlaps among areas of bone tunnel placement found by different studies in near-isometric reconstruction. Not all native anterior cruciate ligament fibers were near-isometric. Conclusion The present study found that the area of femoral bone tunnel of anterior cruciate ligament near-isometric reconstruction were near the anterior part of lateral intercondylar ridge, deeply positioned with longitudinal axis close to the extension line of posterior cortical part of femur, coinciding with the distribution of direct fibers. There was contradiction on whether anterior cruciate ligament near-isometric reconstruction areas and anterior cruciate ligament anatomic insertion sites overlapped with each other. The most isometric area within the anatomic insertion site was the area of anterior fibers near lateral intercondylar ridge, which carried a large portion of the total anterior cruciate ligament load. Generally, there was a scarce of clinical researches in the field of isometry of ACLR. For the purpose of attesting the accuracy of the results we found, a combination of intra-operative observation on the displacement of graft relative to bone-tunnel and post-operative imaging such as MRI and three dimensional CT should be considered.

Objective To evaluate the clinical effect of milrinone nebulized inhalation for improving intraoperative cardiac function and pulmonary arterial pressure in the patients with chronic obstructive pulmonary disease (COPD) complicating pulmonary hypertension (PH).Methods Forty-four surgical patients with COPD complicating PH in the Chongqing Municipal Medical Emergency Center from June 2015 to June 2016 were chosen,including 23 cases of thoracic surgery,13 cases of abdominal surgery and 8 cases of lower extremity fracture surgery.The patients were divided into the control group and treatment group,22 cases in each group.The control group received the routine comprehensive treatment.In addition receiving the conventional comprehensive treatment,milrinone nebulized inhalation in the treatment group was given before general anesthesia.Both of the two groups were imbedded with floating catheter in the right internal jugular vein for detecting the clinical indexes:cardiac output (CO),pulmonary artery systolic pressure (PASP),pulmonary artery mean pressure (PAMP) and pulmonary capillary wedge pressure (PCWP).Results Compared with before treatment,CO after treatment in the treatment group was significantly increased (P＜0.05),PASP,PAMP and PCWP after treatment in the treatment group were significantly decreased(P＜0.05).CO,PASP,PAMP and PCWP in the control group had no statistical difference between before and after treatment,the difference was not statistically significant (P＞0.05).Conclusion Intraoperative milrinone nebulized inhalation in the patients with COPD complicating PH can effectively improve the patient's cardiopulmonary function.

Drosophila dEAAT2, a member of the excitatory amino-acid transporter (EAAT) family, has been described as mediating the high-affinity transport of taurine, which is a free amino-acid abundant in both insects and mammals. However, the role of taurine and its transporter in hearing is not clear. Here, we report that dEAAT2 is required for the larval startle response to sound stimuli. dEAAT2 was found to be enriched in the distal region of chordotonal neurons where sound transduction occurs. The Ca imaging and electrophysiological results showed that disrupted dEAAT2 expression significantly reduced the response of chordotonal neurons to sound. More importantly, expressing dEAAT2 in the chordotonal neurons rescued these mutant phenotypes. Taken together, these findings indicate a critical role for Drosophila dEAAT2 in sound transduction by chordotonal neurons.
Acoustic Stimulation ; Action Potentials ; genetics ; Animals ; Animals, Genetically Modified ; Auditory Pathways ; physiology ; Calcium ; metabolism ; Drosophila ; genetics ; Drosophila Proteins ; genetics ; metabolism ; Excitatory Amino Acid Transporter 2 ; genetics ; metabolism ; Hearing ; genetics ; Larva ; Luminescent Proteins ; genetics ; metabolism ; Mutation ; genetics ; Nervous System ; cytology ; Neurons ; metabolism