Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Nanchang University and Queen Mary University of London have integrated their educational and teaching advantageous resources to establish a Sino-foreign cooperative clinical medicine program in China. The program awards the degrees of Bachelor of Science in Biomedical Sciences and Bachelor of Clinical Medicine, aiming to cultivate well-rounded medical talents with both clinical and scientific research capabilities and an international perspective. By introducing biomedical courses and integrating them with basic medical courses, the program emphasizes basic knowledge, practical training, active learning, and the cultivation of scientific research skills and critical thinking ability. The evaluation parameters include academic output, innovation competitions, and the number of students pursuing graduate education. The results showed substantial increases in the number of SCI academic articles published by students in this program, the number of awards in innovation competitions, and the number of students pursuing graduate education. This program is a new attempt in the reform of medical education in China.

Objective To explore the economic toxicity perceptions and experiences of caregivers of colorectal cancer patients from the perspective of social ecological systems theory.Methods Using purposive sampling,18 caregivers of colorectal cancer patients hospitalized in the gastrointestinal sur-gery and oncology departments of a tertiary grade A hospital in Yangzhou were selected for semi-struc-tured interviews.The Colaizzi 7-step analysis method was employed to organize and analyze the data.Results Three main themes and nine sub-themes were extracted regarding the economic toxicity expe-riences and needs of caregivers of colorectal cancer patients.Microsystem included multiple negative experiences,impacted individual health,and difficulties in surrogate decision-making;mesosystem in-cluded heavy family financial burden,altered family lifestyle,and tense family atmosphere;macrosys-tem included needs for the scope and intensity of medical insurance reimbursement,needs for medical resources and services,and a desire for social support.Conclusion The ecological system of caregiv-ers of colorectal cancer patients is not optimistic,and is generally affected by economic toxicity.Inter-vention strategies can be sought from multiple aspects,including alleviating the negative experiences of caregivers,strengthening social support,and paying attention to the needs of caregivers,aiming to re-duce the level of economic toxicity among caregivers of colorectal cancer patients.

Nanchang University and Queen Mary University of London have integrated their educational and teaching advantageous resources to establish a Sino-foreign cooperative clinical medicine program in China. The program awards the degrees of Bachelor of Science in Biomedical Sciences and Bachelor of Clinical Medicine, aiming to cultivate well-rounded medical talents with both clinical and scientific research capabilities and an international perspective. By introducing biomedical courses and integrating them with basic medical courses, the program emphasizes basic knowledge, practical training, active learning, and the cultivation of scientific research skills and critical thinking ability. The evaluation parameters include academic output, innovation competitions, and the number of students pursuing graduate education. The results showed substantial increases in the number of SCI academic articles published by students in this program, the number of awards in innovation competitions, and the number of students pursuing graduate education. This program is a new attempt in the reform of medical education in China.

Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes.Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/ Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

Objective:To analyze the influential factors of hypoalbuminemia in patients with preeclampsia and observe the pregnancy outcomes.Methods:The clinical data of 237 pregnant women with preeclampsia who received treatment in The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital) from July 2018 to December 2020 were retrospectively collected and analyzed. These patients were divided into hypoproteinemia (observation group) and no hypoproteinemia (control group) groups according to whether they had hypoproteinemia. The general situation, clinical data, and adverse maternal and infant outcomes were statistically analyzed. Risk factors of hypoalbuminemia were analyzed using a logistic regression model. The predictive efficacy was evaluated using the receiver operating characteristic curve.Results:There were no significant differences in general data between the two groups (all P > 0.05). Multivariate analysis showed that D-dimer ( OR = 1.25, P = 0.004), 24-hour urinary protein ( OR = 1.29, P < 0.001), and total bile acid ( OR = 1.08, P = 0.010) were the independent risk factors for hypoproteinemia in preeclampsia. The predictive efficacy of these three indicators (area under the receiver operating characteristic curve = 0.855, P < 0.001) was greater than that of a single indicator. The incidences of adverse maternal and infant outcomes including placental abruption (9.4%, P = 0.019), liver and kidney dysfunction (34.4%, P < 0.001), pleural and ascitic fluid (28.1%, P = 0.001), fetal intrauterine growth restriction (50.0%, P = 0.001), fundus lesions (6.2%, P = 0.018), HELLP syndrome (9.4%, P = 0.019), mild neonatal asphyxia (15.6%, P = 0.022), severe asphyxia (6.2%, P = 0.049), metabolic acidosis (12.5%, P = 0.001), intrauterine infection (12.5%, P = 0.004), and neonatal hospitalization for more than 20 days (37.5%, P < 0.001) were greater in the observation group compared with the control group. There were no significant differences in postpartum hemorrhage, eclampsia, respiratory distress syndrome, fetal loss, and neonatal death between the two groups (all P > 0.05). Conclusion:D-dimer, 24-hour urinary protein, and total bile acid are independent risk factors for hypoproteinemia in preeclampsia. Patients with preeclampsia complicated by hypoproteinemia have a high risk of adverse maternal and infant outcomes.

Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.

Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.

Single-cell proteome analysis can perform in-depth research on cell heterogeneity and further promote the development of precision medicine and tumor research. In recent years, mass spectrometry-based proteomics has made substantial progress, but proteomics analysis at the single-cell level still faces sensitivity challenges. At present, liquid chromatography tandem mass spectrometry has become the main analysis method of proteomics. Because of its high sensitivity, high throughput, and high stability, it has been widely used in the field of single cells. In recent years, the representative single-cell proteomics methods can be divided into three types: single-tube technology, microfluidic platform, and integrated processing platform according to different sample processing methods. Different kinds of data collection and analysis methods have their own advantages and disadvantages. If single-cell proteomics, still a laboratory study, can be applied in diagnostic practice as soon as possible, it will definitely promote the progress of precision medicine and oncology research.

OBJECTIVE: To study the expression of tumor associated vascular insulin receptor (TVIR) in colorectal cancer with or without metabolic syndrome (MS) and its relationship with the pathological features of colorectal cancer. METHODS: The expression of TVIR in 220 colorectal cancer specimens was detected by tissue microarray and immunohistochemistry. The relationships between the expression of TVIR and the pathological features (pathological subtypes, histological grade, invasion depth, lymph node metastasis and TNM stage) of colorectal cancer with/without MS were analyzed. RESULTS: The insulin receptor expression was observed in colorectal cancer tissue or border area between cancer and normal tissue, but not in normal intestinal tissue. The high-expression rates of TVIR in MS group was remarkably lower than that of non-MS group (21.6%vs. 41.0%, CONCLUSIONS s: High-expression of TVIR is associated with aggressive pathological features such as invasion, lymph node metastasis and high TNM stage of colorectal cancer, especially for those patients without MS. TVIR could be a useful biological marker for prognosis of colorectal cancer.
Biomarkers, Tumor/genetics* ; Colorectal Neoplasms/physiopathology* ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; Prognosis ; Receptor, Insulin/genetics*