This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Objective To investigate the related factor underlying the differential vulnerability of inner hair cell(IHC)ribbon synapses to noise exposure.Methods Twenty-eight C57BL/6J mice were randomly divided into the noise exposure group(NED1)and the control group(CTR)with 14 mice in each group.The noise exposure group was exposed to bandpass noise of 2～20 kHz at 103 dB SPL for two hours while the control group was bred in a quiet environment.Before and after noise exposure,auditory brainstem response was conducted to detect the audi-tory function,whole-mount immunofluorescence staining was used to observe the number of inner hair cell ribbon synapses in different turns.The calcium influx of inner hair cells in the apical and middle turn using whole-cell patch clamp recording was analyzed.Furthermore,the immunofluorescence intensity of calpain in inner hair cells from dif-ferent mouse cochlear turns using whole-mount immunofluorescence staining was compared.Western blotting was used to verify that CtBP2 was degraded by calpain.Results After noise exposure,the ABR threshold of 11.3,16.0,22.6,32.0 kHz increased significantly and the number of ribbon synapses of inner hair cells at the middle turn and basal turn of the cochlea decreased significantly.However,whole-cell patch clamp recordings showed that calcium ion channels were fewer but single-channel current was higher at the apical turn of the cochlea.The open probability of calcium ion channels in IHCs showed no significant difference between the apical turn and the middle turn of the cochlea.But the expression level of calpain of the inner hair cells at the middle and basal turn of the basi-lar membrane was significantly higher than that at the apical turn after noise exposure.The western blotting results also showed that CtBP2 was cleaved in a Ca2+-dependent manner by calpain.Conclusion Calpain may be the main related factor that accounts for the vulnerability of ribbon synapses in inner hair cells in the high frequency region of basal membrane.

Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage,using a combination of morphological analysis,and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL(sound pressure level)broadband noise for 2 hours.Auditory brainstem response(ABR)tests were performed on the mice on days 1,7,14,30,and 90 after the noise exposure.Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses,as well as astrocyte activation levels.In addition,the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed.The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons,indicating that noise caused significant damage to cochlear nucleus neurons.Moreover,a significant loss of auditory synapses labeled with vesicular glutamate transporter 1(Vglutl)was observed,which was the severest on day 14 after noise exposure and slowly recovered on day 90.Interestingly,astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure.By staining with glial fibrillary acidic protein(GFAP),most astrocytes were distributed around the cochlear nucleus,granule cell area,and auditory nerve root before noise exposure,and they had a small size.However,on day 14 after noise exposure,a large number of activated astrocytes aggregated in the ventral cochlear nucleus,and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus,and it is possible that astrocytes are involved in its damage and repair processes.These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis,integration,and neural plasticity in the cochlear nucleus.

Objective:Cerebellopontine angle(CPA)tumors are a common cause of secondary trigeminal neuralgia(TN),characterized by their concealed location,slow progression,and difficulty in early detection.This study aims to explore the clinicopathological characteristics of patients with secondary TN due to CPA tumors to enhance understanding and management of secondary TN. Methods:A retrospective analysis was conducted on clinical data and pathological results of 116 patients with CPA tumor-related TN treated at Xiangya Hospital of Central South University from January 1,2017 to December 31,2022.The study analyzed the relationship of tumor pathological types with clinical manifestations,tumor location,surgical methods,and treatment outcomes. Results:Among the cases,95.7％(111/116)were benign tumors,3.4％(4/116)were malignant tumors,and 0.9％(1/116)were borderline tumors.Benign tumors were predominantly acoustic neuromas,meningiomas,and schwannomas.Among the patients,46.6％(54/116)presented with isolated TN,while 53.4％(62/116)exhibited other associated symptoms depending on factors such as tumor growth location and rate.The complete resection rate in this group was over 90％,with 41.4％(48/116)of patients undergoing concurrent microvascular decompression after tumor resection,predominantly for schwannomas.The overall effective rate of surgical treatment reached 93.9％,with schwannomas showing higher efficacy rates compared with acoustic neuromas and meningiomas(P＜0.05).The recurrence rate of acoustic neuromas was significantly higher than that of meningiomas and schwannomas(P＜0.05). Conclusion:CPA tumors are a major cause of secondary TN,predominantly benign,with occasional underdiagnosed malignant tumors.Early diagnosis and treatment significantly impact prognosis.Different tumor types vary in clinical symptoms,surgical approaches,and treatment efficacy.Surgical strategies should balance tumor resection extent and neural function preservation,with microvascular decompression as necessary.

Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
Humans ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B virus/genetics*

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*

Objective: To analyze the current status of work-related musculoskeletal disorders (WMSDs), work fatigue and musculoskeletal pain in Chinese occupational population, and to study the relationship between work fatigue and musculoskeletal pain and WMSDs. Methods: A total of 66 961 employees from 323 enterprises in 15 key industries in China were selected as the study subjects using stratified cluster sampling method. The incidence of WMSDs in the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire, and the work fatigue and musculoskeletal pain were investigated using Borg 6-20 Rating of Perceived Exertion Scale and visual analogue scale. The data were standardized using the age composition data of 18 to 60 years from the seventh national population census. Results: The standardized annual incidence of WMSDs was higher in the front-line workers than that in the administrative and other supportive staff (38.82% vs 36.30%). The detection rates of work fatigue and musculoskeletal pain in the study subjects were 44.54% and 63.08%, respectively. The result of S-curve fitting showed that the risk of WMSDs increased with the level of work fatigue (P<0.01). Among the front-line workers, the average of monthly fatigue frequency in the neck, shoulder, lower back, upper back, wrist/hand, foot and ankle, knee, leg, and elbow were higher in the group with WMSDs compared to those without WMSDs (all P<0.01). The pain degree of musculoskeletal pain was higher in all nine sites in the fatigued group than in the no-fatigue group (all P<0.01). The standardized detection rate of musculoskeletal pain was higher in the fatigued group than in the non-fatigued group (80.38% vs 25.71%). The work fatigue was moderate and positively correlated with musculoskeletal pain in all seven sites except the lower back and elbow, with Kendall Tau-b correlation coefficients ranging from 0.423 to 0.546 (all P<0.01). Conclusion: There is a good correlation between work fatigue and local musculoskeletal pain, work fatigue and WMSDs in Chinese occupational population. Implementing ergonomic interventions to control the development of work fatigue can be an effective measure for preventing WMSDs.

Objective:To evaluate the right ventricular function in patients with dilated cardiomyopathy (DCM) by four-dimensional automatic right ventricular quantitative analysis (4D Auto RVQ), and compare with the right ventricular ejection fraction measured by cardiac magnetic resonance (CMR-RVEF), and to explore the clinical application value of 4D Auto RVQ technique in evaluating the right ventricular function of patients with DCM.Methods:A prospective study was conducted to select 52 patients with DCM who were treated in Fuwai Central China Cardiovascular Hospital of Zhengzhou University from March to October 2022 as DCM group, and 52 healthy volunteers were selected as the control group during the same period. The four-dimensional right ventricular ejection fraction (4D-RVEF), right ventricular stroke volume index (RVSVI), right ventricular end-diastolic volume index (RVEDVI), right ventricular end-systolic volume index (RVESVI), four-dimensional right ventricular basal diameter (4D-RVDd-base), four-dimensional right ventricular middle diameter (4D-RVDd-mid), four-dimensional right ventricular long axis diameter (4D-RVLd), four-dimensional tricuspid annular plane systolic excursion (4D-TAPSE) and four-dimensional right ventricular fractional area change (4D-RVFAC) were obtained by 4D Auto RVQ technique. The differences of the above parameters between DCM group and control group were compared.Pearson linear correlation analysis was used to evaluate the correlation between echocardiographic parameters and CMR-RVEF. The ROC curve was used to find the most sensitive parameters for evaluating right ventricular function, and the area under the ROC curve ( AUC ) was calculated and compared.Results:Compared with the control group, RVEDVI, RVESVI, 4D-RVDd-base and 4D-RVDd-mid in the DCM group were increased, and the absolute values of 4D-RVEF, 4D-TAPSE, 4D-RVFAC, right ventricular global longitudinal strain(RVGLS) and right ventricular free wall longitudinal strain(RVFWLS) were decreased (all P<0.05). Correlation analysis showed that 4D-RVEF was positively correlated with CMR-RVEF ( r=0.711, P<0.05). ROC curve analysis showed that 4D-RVEF was superior to other parameters in evaluating right ventricular function in DCM patients (AUC: 0.916). Conclusions:4D Auto RVQ technique can quantitatively evaluate right ventricular function in DCM patients. 4D-RVEF has a significant correlation with CMR-RVEF, and 4D-RVEF has the best efficacy in evaluating right ventricular function in DCM patients.

Objective:To evaluate left atrial(LA) function and its value in predicting left ventricular(LV) remodeling in patients with coronary heart disease (CHD) by four dimensional automatic left atrial quantitation (4D Auto LAQ).Methods:A total of 176 patients with CHD were prospectively enrolled in Fuwai Central China Cardiovascular Hospital from October 2021 to September 2022. They were divided into two groups according to left ventricular mass index: LV remodeling group (female>95 g/m 2, male>115 g/m 2, n=88) and Non-LV remodeling group (female≤95 g/m 2, male≤115 g/m 2, n=88). The 3D dynamic image of LA was analyzed by 4D Auto LAQ on machine to obtain the LA parameters, including the minimum, maximum, pre-systolic and emptying volumes of LA (LAVmin, LAVmax, LAVpreA, LAEV), LA ejection fraction (LAEF), LA reservoir longitudinal and circumferential strains (LASr, LASr-c), LA conduit longitudinal and circumferential strains (LAScd, LAScd-c) and LA contraction longitudinal and circumferential strains (LASct, LASct-c). Logistic regression models were used to analyze the value of LA parameters in predicting LV remodeling in patients with CHD. ROC curve was used to evaluate LA parameters and left atrial volume index (LAVI) to predict the diagnostic efficiency of LV remodeling. Results:Compared with the Non-LV remodeling group, LAVmin, LAVmax, LAVpreA were significantly increased and LAEF, LASr, LAScd, LASct, LASr-c, LAScd-c, LASct-c were significantly decreased in the LV remodeling group ( P<0.05). Logistic regression model showed that LASct-c was an independent risk factor for LV remodeling in patients with CHD after adjustment( OR=2.018, 95% CI=1.214-3.355). ROC curve analysis showed that the area under the curve of LASct-c for predicting LV remodeling in CHD patients was 0.844, the sensitivity was 0.784, and the specificity was 0.761. Conclusions:4D Auto LAQ can effectively evaluate LA function in patients with CHD.LASct-c can be used as a reference index to predict LV remodeling in patients with CHD, which provides a new evaluation method in prognosis evaluation of CHD patients.