[Drought and Heat Stress-Mediated Modulation of Alternative Splicing in the Genes Involved in Biosynthesis of Metabolites Related to Tea Quality].

Alternative splicing (AS) regulates mRNAs at the post-transcriptional level to affect both their amounts and the protein function. However, little is known about the roles of AS in regulation of biosynthesis of amino acids, flavonoids, and volatile compounds in tea plants. In this study, we used Iso-seq and transcriptome deep sequencing (RNA-seq) to identify AS events, and analyzed the expression of respective mRNAs in tea plants under drought (DS), heat stress (HS), and their combination (HD). By RT-PCR, we validated the AS events in nine genes involved in the biosynthesis of amino acids and flavonoids. The genes accumulating AS transcripts under DS, HS, and HD conditions included those encoding for anthocyanidin reductase (ANR), dihydrofavonol-4-reductase-like (DFRA), and chalcone isomerase (CHI). Similarly, genes directly or indirectly involved in the biosynthesis of volatile compounds such as lipoxygenase (LOX), terpenoid/terpene synthase (TPS), and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) also had AS events. Our study revealed that AS might specifically regulate the biosynthesis of amino acids in tea plants under stressful conditions. Moreover, we suggest that the AS events within the ANR and DFRA transcripts might play an important role in the regulation of flavonoid biosynthesis under DS, HS, and HD conditions. This study improved our understanding of the genetic drivers of the changes in the content of bioactive ingredients of tea plants subjected to abiotic stresses.

[Clinical analysis of 46 rheumatoid arthritis patients with peripheral neuropathy].

Objective: To study clinical features of rheumatoid arthritis (RA) patients with peripheral neuropathy (PN). Methods: The clinical data of 46 RA patients with PN in the First Affiliated Hospital of Zhengzhou University from August 2012 to August 2019 were retrospectively analyzed, including clinical manifestations, laboratory and imaging results, previous treatment, treatment and clinical outcome. The other 92 RA patients without PN at the same period were selected as controls. Results: In RA patients with PN, the male to female ratio was 1∶2.1 with an average age (59.1±11.8) years. The course of RA and PN was 102.0 (19.0-156.0) months and 4.2 (0.7-5.5) months respectively. Numbness (84.8%, 39/46) and muscle weakness (21.7%, 10/46) were the most common symptoms. According to results of electromyography, polyneuropathy (60.0%, 27/46) was the predominant manifestation, followed by mononeuritis multiplex (31.1%, 14/46). Compared to RA patients, rheumatoid factor (RF) (P<0.001) and the percentage of cutaneous vasculitis (P=0.042) were higher in RA patients with PN. Logistic regression analysis revealed significant correlation between RF>178.4 IU/ml (OR＝5.626, 95%CI 2.509-12.618, P<0.001) and development of PN. Paresthesia in 27 patients (58.7%, 27/46) were relieved after treatment of high dose glucocorticoid and immunoglobulins (IVIG). Twelve patients were followed up regularly and the mean duration of follow-up was 17.0(4.8-52.8)months. Paresthesia in 10 (10/12) patients were relieved compared to that at discharge, 1 (1/12) patient achieved complete remission. Conclusion: Numbness and muscle weakness are the common symptoms in RA patients with PN and polyneuropathy is the main type. RF>178.4 IU/ml is correlated with the development of PN in RA patients. Intensive treatment such as high dose glucocorticoid and IVIG are effective.

[Application of artificial intelligence-assisted diagnosis for cervical liquid-based thin-layer cytology].

Objective: To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening. Methods: A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao'an People's Hospital(Group) and Changsha Yuan'an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared. Results: The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual. Conclusions: Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.

[A Qualitative Proteome-Wide Lysine Succinylation Profiling of Tea Revealed its Involvement in Primary Metabolism].

Lysine succinylation of proteins has potential impacts on protein structure and function, which occurs on post-translation level. However, the information about the succinylation of proteins in tea plants is limited. In the present study, the significant signal of succinylation in tea plants was found by western blot. Subsequently, we performed a qualitative analysis to globally identify the lysine succinylation of proteins using high accuracy nano LC-MS/MS combined with affinity purification. As a result, a total of 142 lysine succinylation sites were identified on 86 proteins in tea leaves. The identified succinylated proteins were involved in various biological processes and a large proportion of the succinylation sites were presented on proteins in the primary metabolism, including glyoxylate and dicarboxylate metabolism, TCA cycle and glycine, serine and threonine metabolism. Moreover, 10 new succinylation sites were detected on histones in tea leaves. The results suggest that succinylated proteins in tea plants might play critical regulatory roles in biological processes, especially in the primary metabolism. This study not only comprehensively analyzed the lysine succinylome in tea plants, but also provided valuable information for further investigating the functions of lysine succinylation in tea plants.

[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment].

COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases had been found. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases,authors proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which were related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.

FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer.

BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay. The in vitro and in vivo function of COMMD10 in CRC was evaluated using CCK-8 proliferation assay, plate colony formation, cell cycle, apoptosis and animal models. The inhibition of NF-κB signalling by COMMD10 was detected using dual-luciferase reporter assay and western blotting. Co-IP, GST pull-down and nuclear protein extraction assay were performed to evaluate the effect on p65 by COMMD10. Real-time PCR and western blotting were performed to detect expressions of FMNL2, COMMD10 and p65 in paired tissues. RESULTS: FMNL2 targets COMMD10 for ubiquitin-mediated proteasome degradation in CRC cells. COMMD10 targets p65 NF-κB (nuclear factor-κB) subunit and reduces its nuclear translocation, thereby leading to the inactivation of NF-κB pathway and suppression of CRC invasion and metastasis. Inhibition of NF-κB signalling by COMMD10 is necessary for FMNL2-mediated CRC cell behaviours. Downregulation of COMMD10 predicts poor prognosis of CRC patients. The expressions of FMNL2, COMMD10 and p65 are highly linked in CRC tissues. CONCLUSIONS: These data demonstrate that the FMNL2/COMMD10/p65 axis acts as a critical regulator in the maintenance of metastatic phenotypes and is strongly associated with negative clinical outcomes.

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.

BACKGROUND: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC. METHODS: The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens. RESULTS: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens. CONCLUSIONS: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

Sunitinib modulates the radiosensitivity of esophageal squamous cell carcinoma cells in vitro.

This study aims to explore the radiosensitivity of sunitinib on esophageal cancer cell lines. For in vitro studies, human esophageal squamous cell carcinoma (ESCC) cell lines were treated with sunitinib 24 hours before irradiation. ESCC cell lines were treated with sunitinib with or without radiation. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis and cell cycle analysis were detected by flow cytometry. Deoxyribonucleic acid (DNA) double-strand breaks were performed by immunocytofluorescence analysis. Western blot analysis was used to determine the effect of sunitinib on radiation induced signal transduction. Sunitinib potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.13-1.72. Furthermore, sunitinib increased radiation induced DNA double-strand breaks, promoted the apoptosis of ESCC cells and induced the G2/M arrest. Radiosensitization was accompanied with enhanced apoptosis and regulated by the intrinsic pathway of apoptosis. Sunitinib sensitized ESCC cells to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in esophageal cancer.

Diversity and potential application of endophytic bacteria in ginger.

Here, 248 endophytic bacterial strains were isolated to assess the distribution and population diversity of endophytic bacteria in ginger plants. A total of 10.4 x 10(4) to 20.2 x 10(4) CFU/g fresh weight endophytic bacteria of different growth stages were isolated. Maximum bacterium numbers were obtained at the seedling stage. A total of 107 functional strains were screened, including 17 antibacterial strains and 90 indole acetic acid-producing strains. Based on 16S rDNA sequence restriction fragment length polymorphism and 16S rDNA sequences, these 107 strains were mapped and grouped into 16 genera. Bacillus and Pseudomonas were the dominant genera; however, the bacteria belonged to a tremendous range of genera, with the highest species richness being observed at the seedling stage. Sixteen strains exhibited antimicrobial activity against Pythium myriotylum Drechsler, while 7 strains exhibited antimicrobial activity against Phyllosticta zingiberi Hori. Bacillus was the dominant antibacterial strain. Pseudomonas fluorescens, B. megaterium, and Enterobacter ludwigii produced remarkably high levels of IAA. Only a few endophytic bacterial strains were inhibited in fresh ginger juice. Most of these strains were present during seedling stage, including Roseateles depolymerans, Chryseobacterium taiwanense, E. ludwigii, Agrobacterium larrymoorei, P. fluorescens, and Bacillus amyloliquefaciens. This study indicates that the community of endophytic bacteria in ginger changes with the synthesis of antibacterial substances.

[Prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China].

Objective: To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China. Methods: A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described. Results: The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age (P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area (P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions: The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.

Homogeneous high attenuation renal cysts and solid masses--differentiation with single phase dual energy computed tomography.

AIM: To assess the feasibility of using single-phase dual-energy computed tomography (DECT) to differentiate between homogeneous high attenuation renal cysts and solid renal masses. MATERIALS AND METHODS: Twenty-nine pathologically proven solid renal masses in 29 patients and 14 high attenuation renal cysts from 11 patients were evaluated retrospectively. Two readers independently measured CT values from each lesion using both unenhanced single-energy phase and nephrographic dual-energy phase scans. Enhancement was defined as the attenuation difference between average-weighted 120 kV images and unenhanced images. Diagnostic sensitivity, specificity and accuracy based on enhancement, D-value (CT: 80 kV-140 kV) and DE-ratio (CT: 80/140 kV) were compared by the receiver operator characteristic (ROC) curves. RESULTS: Using 17.6 HU as the cutoff value for enhancement, resulted in a sensitivity, specificity and accuracy of 96.6%, 100% and 97.7%, respectively. Corresponding values were 100%, 92.9% and 97.7% using a D-value cutoff of 15.6 HU, and 100%, 85.7% and 95.3% using a DE-ratio cutoff of 1.3. There were no significant differences in the AUCs obtained from the ROC curves for enhancement, D-value or DE-ratio. The mean effective radiation dose was 6.04 mSv with biphasic scanning compared with 2.91 mSv for single dual-energy nephrographic phase scanning. CONCLUSION: Single-phase dual-energy CT is able to differentiate high attenuation renal cysts and solid renal masses with high sensitivity, specificity and accuracy, based on either D-value or DE-ratio. Omitting unenhanced scanning reduces the radiation dose by more than 50%.

[A review on cardiovascular disease risk prediction models in the elderly].

Risk prediction models play an important role in the primary prevention of cardiovascular diseases (CVD) in the elderly population. There are fifteen papers about CVD risk prediction models developed for the elderly domestically and internationally, of which the definitions of disease outcome vary widely. Ten models were reported with insufficient information about study methods or results. Ten models were at high risk of bias. Thirteen models presented moderate discrimination in internal validation, and only four models have undertaken external validation. The CVD risk prediction models for the elderly differed from those for the general population in terms of model algorithm and the effect size of association between predictor and outcome, and the prediction performance of the models for the elderly attenuated. In the future, high-quality external validation researches are necessary to provide more solid evidence. Different ways, including adding new predictors, using competing risk model algorithms, machine learning methods, or joint models, and altering the prediction time horizon, should be explored to optimize the current models.

Personalized music therapy combined with medication as treatment for tinnitus.

OBJECTIVE: This study aimed to investigate the effects of personalized music therapy in combination with medication as a treatment for tinnitus. PATIENTS AND METHODS: We retrospectively analyzed a total of 200 patients who were admitted to the Department of Otorhinolaryngology in our hospital from June 2018 to June 2019, with tinnitus as their primary complaint. Patients were divided into four groups based on their individual treatment methods: medication group (patients received medication only, n=40), tinnitus masking (TM) group (patients received medication plus TM, n=38), tinnitus re-training (TRT) group (patients received medication plus TRT, n=35), and personalized group (patients received medication plus personalized music therapy, n=30). The pure-tone audiometry (PTA), loudness visual analogue scale (VAS), and tinnitus handicap inventory (THI) for each patient were analyzed. RESULTS: There were statistically significant differences in the THI and VAS scores of all groups before and after treatment (p<0.05). Following nine and twelve months of treatment, the THI and VAS scores of the TRT group and the personalized group were significantly lower than those of the other two groups (p<0.05). The THI and VAS scores of the personalized group were significantly lower than those of the TRT group (p<0.05). Additionally, THI and VAS scores were statistically different at various measurement time points in each group (p<0.05). The clinical effective rate (85.37%) of the personalized group was higher than that of the other three groups (p<0.05). CONCLUSIONS: TM, TRT, or personalized music therapy, when combined with medication, are effective in treating patients with tinnitus. Among these methods, personalized music therapy may be the superior treatment after nine months of treatment.

Epstein-Barr virus-associated pneumonia in patients with post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation or infection after hematopoietic stem cell transplantation (HSCT) most often induces post-transplant lymphoproliferative disease (PTLD), but it also may be associated with clinical symptoms such as pneumonia. Our aim was to investigate and describe the clinical manifestations of PTLD and PTLD accompanied by EBV-associated pneumonia in 323 patients after HSCT. PTLD within extravisceral lymphoid tissue was identified in 7 cases (5 with CD20(+) diffuse large B-cell lymphoma, 1 with CD20(+) polymorphic B-cell hyperplasia, and 1 with CD3(+)CD45RO(+) peripheral T-cell lymphoma unspecified). Six of the patients with PTLD were EBV positive. Three patients had EBV-associated pneumonia, and chest computed tomography revealed multifocal patchy and diffuse ground-glass attenuation in both lungs. EBV-DNA was positive in bronchoalveolar lavage (BAL) fluid, which contained mainly CD3(+) T cells but no CD19(+) or CD20(+) B cells. Lung biopsy showed interstitial intra-alveolar infiltrates of mainly CD3(+) T cells and some CD68(+) macrophages without CD19(+) and CD20(+) B cells. The patients with PTLD accompanied by EBV-associated pneumonia developed hyperpyrexia and dyspnea, which progressed rapidly, and eventually all died within 2 weeks of the onset of PTLD. EBV-associated PTLD accompanied by EBV-associated pneumonia after HSCT is rare. Cytology of BAL fluid and lung biopsy may help establish the diagnosis.