Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Objective To analyze and compare the auxiliary value and significance of γ-interferon release assay (IGRA) in the diagnosis of tuberculosis. Methods A retrospective analysis was conducted to collect the test results of 462 suspected tuberculosis patients who underwent IGRA detection in the outpatient department of Tianjin Tuberculosis Control Center from January 2020 to December 2021. According to the diagnostic results, they were divided into a tuberculosis group of 229 cases (203 cases of pulmonary tuberculosis and 26 cases of extrapulmonary tuberculosis) and a non-tuberculosis group of 233 cases. The auxiliary diagnostic value of IGRA for tuberculosis was analyzed and compared with two methods of Mycobacterium tuberculosis culture and Xpert MTB/RIF. Results The positive rates of IGRA, Mycobacterium tuberculosis culture, and Xpert MTB/RIF in TB patients were 76.42%, 29.26% and 40.62%, respectively, compared with the non-TB group (38.20%, 0.00%, 0.00%), with statistically significant differences (P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of IGRA alone in the detection of tuberculosis were 76.42%, 61.80%, 69.29%, and 72.73% respectively, those of Mycobacterium tuberculosis culture were 29.26%, 98.28%, 94.37%, and 63.43%, and those of Xpert MTB/RIF were 40.60%, 100%, 100%, and 63.14%. The positive rates of IGRA were 76.85% and 73.08% in patients with pulmonary tuberculosis and extrapulmonary tuberculosis, respectively, with no statistical significance (P>0.05). The positive rates of IGRA in bacterial positive patients and non-tuberculosis patients were 79.34% and 38.20%, respectively, with statistical significance (χ2=54.526, P<0.001). The positive rates of IGRA in patients with and without tuberculosis were 73.15% and 38.20%, respectively, with significant difference (χ2=36.456, P<0.001). Conclusions IGRA has a relatively high sensitivity in the diagnosis of tuberculosis and also has certain advantages in the screening of extrapulmonary tuberculosis and mycobacterium-negative It provides important reference basis for the clinical diagnosis of tuberculosis.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment.Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Objective: To investigate the association between maternal parenting styles and quality of life among preschools，to provide a scientific theoretical basis for interventions targeting at prmoting early life health. Methods: From May to July, 2021, a stratified cluster sampling method was used to enroll 4 233 child mother dyads from 14 preschools in Chengdu. An online questionnaire survey was administered to collect socio demographic information, maternal parenting styles, and children s quality of life. Results: The overall score of quality of life was (80.17±9.81) among preschool children in Chengdu. In the multivariate linear regression models, maternal emotional warmth were significantly associated with higher scores in emotional functioning, social functioning, school functioning, psychosocial health summary score, and total scores ( β coefficients in the high level group were 2.63 , 4.95 , 12.05, 6.54,4.88, P <0.05). In contrast, both maternal rejection and overprotection were significantly associated with lower scores in physical functioning, emotional functioning, social functioning, school functioning, psychosocial health summary score, and the total scores of children s quality of life (for rejection: β coefficients in the high level group were -9.39, -10.82, -7.12 , -6.04 , -8.00, and -8.35 , respectively; for overprotection: β coefficients in the high level group were -6.71, -5.85, -3.08 , -2.39 , -3.77, and - 4.51 , respectively， P <0.05). The associations between high level of maternal rejection and children s emotional functioning showed significant gender differences( β =-3.23, P <0.05). Conclusion Maternal parenting style has a significant impact on children s quality of life. Interventions targeting at maternal parenting styles may be beneficial to improve the quality of life in preschool children.

Objective To compare the effects of different respiratory signal acquisition methods on the delineation of moving tumor targets. Methods A cube phantom containing a sphere was placed on a motion platform to simulate respiratory movement by setting motion period, frequency, and direction. Respiratory signal was acquired by real-time position management (RPM) method and GE method independently. Target delineation was conducted using the maximum intensity projection (MIP) sequence. The difference between the reconstructed volume and the theoretical moving volume was compared under the two respiratory signal acquisition methods for cube and sphere targets. Results Under the same respiratory signal acquisition method, the same respiratory amplitude, and different respiratory frequencies, reconstructed volume changes were relatively small. For the sphere target, the deviation between the reconstructed volume and the theoretical moving volume was −1.5% to 5.7% with the RPM method and −1.3% to −13.8% with the GE method (both P < 0.05). For the cube target, the deviation between the reconstructed volume and the theoretical moving volume was 0.2% to 0.9% with the RPM method and −2.6% to 0.9% with the GE method, with no statistical significance. Conclusion For small-volume sphere targets, the target volumes obtained from MIP images by the two respiratory signal acquisition methods are both smaller than the actual moving volume. For large-volume cube targets, there is no significant difference between the reconstructed and theoretical results with any respiratory signal acquisition method. The RPM method produces smaller deviation and better image quality when reconstructing small-volume targets.

Objective    To summarize the clinical result of a combined technical system for bicuspid aortic valve (BAV) repair. Methods    Patients who diagnosed as BAV and sever aortic regurgitation (AR) underwent a strategy of combined repair technics including annuloplasty, sinus plasty, leaflet plasty, sinus-tubular junction (STJ) plasty depending on anatomy pathological characteristics between October 2019 and January 2021 were enrolled. The clinical data of the patients were analyzed. Results    A total of 17 patients were enrolled. There were 11 males and 6 females with an average age of 18-49 (32.4±13.6) years. Fifteen patients had typeⅠand 2 patients had typeⅡBAV according to Sievers classification. Annuloplasty was applicated in 13 patients, sinus plasty in 8 patients, leaflet plasty in 17 patients, and STJ plasty in 11 patients, respectively. The cardiopulmonary bypass (CPB) time was 95 (84, 135) min, aortic cross-clamping time was 68 (57, 112) min, and the ICU stay time was 17 (12, 25) h. After the operation, mild AR was presented in 14 patients, moderate AR in 1 patient and severe AR in 2 patients. The latter 3 patients underwent second operation under CPB, after then, 1 patient had mild AR and 2 patients had moderate AR. The follow-up time was 13.1±4.6 months. At the latest follow-up, 12 patients had mild AR and 5 patients had moderate AR, and no patient had reoperation. Conclusion    A combined technical system for BAV repair can be used effectively and safely with an acceptable short and middle-term result.

OBJECTIVE To compare the efficacy， safety and economy of tacrolimus （TAC）， cyclosporin A （CsA）， cyclophosphamide （CTX） and rituximab （RTX） in the treatment of membranous nephropathy （MN）. METHODS Retrieved from Pubmed， the Cochrane Library， Wanfang data， CNKI and health technology assessment （HTA） official website， HTA reports， systematic reviews/meta-analysis and pharmacoeconomic studies about TAC， CsA， CTX and RTX combined with glucocorticoid in the treatment of MN were collected during the inception and Mar. 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS A total of 15 articles were included， involving 13 systematic reviews/meta-analysis and 2 pharmacoeconomic studies. In terms of efficacy， TAC and CsA showed significant advantages in increasing the response rate， and could improve the levels of urine protein， serum albumin， serum creatinine and serum total cholesterol. In terms of safety， the incidence of adverse reaction induced by TAC， CsA and RTX was low and the symptoms were mild. In terms of economics， CTX cost lower but caused severe adverse reaction； TAC cost higher but showed higher remission rate and good safety. CONCLUSIONS TAC combined with glucocorticoid may be the recommended scheme for MN.

Objective:To compare the dosimetric differences between the VenusX accelerator with an orthogonal dual-layer multi-leaf collimator (MLC) and the Varian′s CLINAC IX and EDGE accelerators with a single-layer MLC for hippocampus protection in the whole-brain radiotherapy (WBRT).Methods:Forty patients with multiple brain metastases admitted to the Radiotherapy Department of the Shanghai General Hospital from June 2021 to February 2023 were selected in this study. Three whole-brain treatment plans were designed based on the above three accelerators for each patient. Under the same prescription dose, radiation field, and plan constraints, the three plans were compared in terms of the dosimetric differences in target volumes, hippocampi, and adjacent organs at risk (OARs), as well as the execution efficiency.Results:For the planning target volume (PTV), there were statistically significant differences in approximate maximum dose ( D2) between the VenusX and IX plans ( t = 4.94, P < 0.05), in approximate minimum dose ( D98) between the VenusX and EDGE plans ( t = 5.98, P < 0.05), in the target conformity indices (CIs) between VenusX plan and EDGE plans, and between the VenusX and IX plans ( t = -6.84, -14.30; P < 0.05), and dose homogeneity indices (HIs) between the VenusX and IX plans ( t = 3.48, P < 0.05). For OARs, the maximum doses ( Dmax) and average doses ( Dmean) to bilateral hippocampi of the VenusX plan were lower than those of the EDGE and IX plans ( t = 8.59-17.11, P < 0.05); the maximum doses ( Dmax) to bilateral lenses, bilateral optic nerves, and optic chiasma of the VenusX plan were lower than those of the other two plans ( t = 2.10-20.80, P < 0.05); and the differences between the maximum doses ( Dmax) to the brain stem of the VenusX and EDGE plans were statistically significant ( t = 3.86, P < 0.05). In terms of plan execution efficiency, the number of machine jumps (MU) and the treatment time of the VenusX plan were higher than those of the EDGE and IX plans, with statistically significant differences ( t = -56.48, -56.90, P < 0.05). Conclusions:The doses to target volumes of the three treatment plans all meet the prescription requirements, and the VenusX plan outperforms the EDGE and IX plans in the protection of OARs. Despite the reduced execution efficiency, the VenusX plan shortens the actual treatment time by improving the dosage rate, thus meeting the clinical requirements.

OBJECTIVE To observe the efficacy and safety of albumin-bound paclitaxel in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Clinical data of patients with advanced NSCLC treated in our hospital from January 2018 to December 2021 were selected. According to their chemotherapy regimen，they were divided into albumin-bound paclitaxel group and paclitaxel group， with 100 patients in each group. Both groups received chemotherapy regimen containing Paclitaxel for injection （albumin-bound） or Paclitaxel injection for at least 2 cycles （every 21 days as a cycle）. The progression-free survival （PFS） and efficacy of the two groups were compared，and the occurrence of toxic and side effects were recorded. RESULTS The patients in albumin-bound paclitaxel group completed 430 cycles of chemotherapy， with an average of 4.3 cycles； patients in paclitaxel group completed 476 cycles of chemotherapy， with an average of 4.8 cycles. The median PFS （4.0 months） and the response rate （13.00%） of albumin-bound paclitaxel group were not significantly different from those of paclitaxel group （4.0 months，9.00%） （P＞0.05）. The disease control rate （99.00%） was significantly higher than that in paclitaxel group （89.00%）， and the incidences of leukopenia， neutropenia， thrombocytopenia，anemia， sensory neuropathy， fatigue，nausea and vomiting，joint myalgia in albumin-bound paclitaxel group were significantly lower than those in paclitaxel group （P＜0.05）. CONCLUSIONS Albumin-bound paclitaxel is effective in the treatment of advanced NSCLC， and it can better control the progression of the disease and is safer than ordinary paclitaxel.