Reproductive toxicology is a discipline that uses toxicological methods to study the mechanisms by which foreign substances interfere with the generation of eggs or sperm and their detrimental effects on offspring. Research includes evaluating the damaging effects of test substances on reproductive function of parents and the toxicity evaluation of offspring embryos. People are exposed to a wide range of drugs, chemicals and environmental pollutants on a daily basis, and determining whether these substances have reproductive toxicity is crucial for the health of future generations. Reproductive toxicology research is therefore critical. Given the specificity and importance of reproductive toxicity evaluation, corresponding institutions both domestically and internationally have issued guidelines, national standards, or industry standards, all of which involve animal experiments. In the study of reproductive system diseases, numerous animal models have been developed to investigate key reproductive organs, such as testicles and ovaries. Each model involves the selection of animals, the establishment of methods, and the quantification of evaluation indicators, and all have advantages and limitations. The choice of model should be based on experimental needs and the characteristics of the model. This paper summarizes commonly used animal models for reproductive and development toxicity evaluation in reproductive toxicology research, including rat models for fertility and early embryonic development toxicity, rat models for embryo-fetal development toxicity, rabbit models for embryo-fetal development toxicity evaluation, minipig models for embryo-fetal development toxicity, rat models for perinatal toxicity, zebrafish models for embryonic development toxicity, and models for evaluating ovarian toxicity induced by chemical drugs, radiotherapy, autoimmunity, and ovariectomy, as well as models for evaluating testicular toxicity caused by chemical drugs and environmental factors. The methods for establishing these models, their application scope, and characteristics are reviewed in order to provide references for relevant research applications.

Pseudorabies virus(PRV)is the etiological agent of pseudorabies in pigs,which is char-acterized by dyspnea,reproductive disorders,and neurological diseases,and it spreads widely a-round the world.Since 2011,the newly emerged PRV variants have resulted in poor immunity pro-tection of traditional vaccine strains,and the original method of vaccine strain preparation is time-consuming and labor-intensive.Therefore,it is urgently needed to develop an efficient screening method of the vaccine strain at present.Using CRISPR/Cas9 gene editing technology in this study,two single guide RNAs(sgRNA)were designed targeting the virulence gene TK of PRV variant strain CH/JX/2016,and then the enhanced green fluorescent protein the reporter(EGFP)gene was inserted at the TK locus by a homologous repair plasmid.After multiple rounds of plaque puri-fication,the rPRV-ΔTK/EGFP strain was obtained.The results showed the cleavage efficiency of the two sgRNAs was extremely high.The preparation of rPRV-ΔTK/EGFP strain was succeed af-ter only three rounds of purification,and the EGFP expressed normally.The CRISPR/Cas9 system can edit the PRV gene simply,rapidly,and efficiently,and exhibits great potential in the construction of vaccine candidate strains.Meanwhile,the rescued rPRV-ΔTK/EGFP strain not only could be used as a tracer strain in PRV variant infection progresses,but also for subsequent antivi-ral drug screening.

Objective:To evaluate the clinical efficacy of intermittent theta burst stimulation (iTBS) of the bilateral cerebellum in treating post-stroke dysphagia.Methods:Forty patients with dysphagia after a cerebral infarction were randomly divided into a control group and an iTBS group, with 20 cases in each group. In addition to routine swallowing rehabilitation training and nutritional guidance, the iTBS group underwent daily bilateral cerebellar iTBS 6 times a week for 3 weeks, while the control group was given sham stimulation. Before and after the treatment, both groups were evaluated by using the water-swallowing test and the standardized swallowing assessment (SSA), and the latency and amplitude of the mylohyoid muscle′s motor evoked potential (MEP) were also recorded. The SSA scores and MEP amplitudes of the mylohyoid muscle after treatment were tested for any correlation.Results:The treatment improved the water-swallowing test results in both groups, with that of the iTBS group significantly better than that of the control group. The clinical efficacy in the iTBS group was 95%, significantly higher than the control group′s 80%. The SSA scores decreased significantly in both groups after the treatment, with the iTBS group′s average score then significantly lower than that of the control group. The average latency and amplitude of the mylohyoid muscle′s MEP was also significantly better in the iTBS group after the treatment. In the control group only the average amplitude was significantly greater than before the treatment. Pearson correlation analysis showed that the SSA scores and the MEP amplitudes of the mylohyoid muscle after treatment were uncorrelated in both groups.Conclusions:Bilateral intermittent theta burst stimulation can effectively improve the swallowing of patients with post-stroke dysphagia.

Objective:Voice is a vital tool for human communication, and its health spans across various stages of an individual's life cycle. This article discuss the importance of voice health from a lifecycle perspective, exploring the needs of voice, phonatory organ changes, the main etiologies and their incidence, the impact on social function, and treatment of voice disorders at different stages （childhood, adolescence, adulthood, and old age）. During childhood, due to incomplete vocal cords development and weak behavioral control, the incidence of voice disorders is high, which adversely affects children's psychological and social function development. The most common condition is vocal nodules, and there has been insufficient attention to the treatment of voice disorders in this stage. Voice disorders during adolescence are mainly related to physiological development and hormonal changes. In the elderly, the larynx undergoes structural and functional aging, which can be delayed with active intervention and treatment. Therefor, maintaining voice health should focus on preventing and managing voice problems throughout the entire life cycle, with targeted voice care and intervention at each stage. Establishing a comprehensive voice health management framework thereby upholds an individual's optimal health status and social function.
Humans ; Voice Disorders/etiology* ; Adolescent ; Child ; Adult ; Voice/physiology* ; Voice Quality ; Vocal Cords ; Aging/physiology* ; Aged

【Objective】 To compare the supply data of red blood cells(RBCs) from 18 blood centers in China before and after the outbreak of COVID-19 during 2018 to 2021. 【Methods】 Eight indicators related to RBCs supply from 18 blood centers in China during 2018-2021 were collected retrospectively, including the storage of total amount of qualified RBCs (referred to as the total amount of storage), the distribution of total amount of RBCs (referred to as the total amount of distribution), the distribution amount of RBCs per 1 000 population (referred to as the amount of distribution per 1 000 population), the distribution amount of RBCs from 400 mL original blood per 1 000 population [referred to as the amount of distribution per 1 000 population (400 mL)], the average daily distribution amount of RBCs (referred to as the average daily distribution amount), the average daily storage amount of RBCs (referred to as the average daily storage amount), the average storage days of RBCs when distribute (referred to as the RBC storage days), and the expired amount of RBCs (referred to as the expired amount). Based on the outbreak time of COVID-19, the data of 2018 and 2019 were the pre-pandemic group, and the data of 2020 and 2021 were the post-pandemic group. 【Results】 Data on RBCs supply in 18 blood centers from 2018 to 2021(comparison of the pre-pandemic group and the post-pandemic group): the amount of distribution per 1 000 population (median 14.68 U>13.92 U) decreased, the amount of distribution per 1 000 population (400 mL) (median 10.16 U>9.21 U) decreased, and the difference was statistically significant (P<0.05); data comparison between 2019 and 2020:the total amount of distribution (median 117 770.38 U>99 084.08 U) decreased, the amount of distribution per 1 000 population (median 15.04 U>12.19 U) decreased, the amount of distribution per 1000 population (400 mL) (median 10.11 U>8.94 U), the average daily distribution amount(322.66 U>270.73 U) decreased and RBC storage days (median 10.50 d<11.45 d) increased, the difference has statistical significance (P<0.05); data comparison between 2020 and 2021:the total amount of storage (median 101 920.25 U<120 328.63 U), the total amount of distribution (median 99 084.08 U<118 428.62 U), the amount of distribution per 1 000 population (median 12.19 U<15.00 U), the amount of distribution per 1 000 population (400 mL) (median 8.94 U<9.46 U), the average daily distribution amount (270.73 U>324.46 U), the average daily inventory (median 3 222.00 U<4 328.00 U) increased, the expired amount (median 1.50 U>0.00 U) decreased, the difference has statistical significance (P<0.05). The results of ANOVA showed that there were significant differences on the data related to RBCs supply (except expired amount) in different blood centers (P<0.05). The ratio of average daily stock to average daily distribution in the post-outbreak group (median 12.36 d) was higher than that in the pre-outbreak group (median 10.92 d), the difference has statistical significance (P<0.05), with significant difference among different blood centers (P <0.05). 【Conclusion】 The COVID-19 pandemic has a significant impact on RBCs supply in different blood centers. In the second year of the pandemic, the supply capability had recovered to some extent, and there were differences in RBCs supply in different blood centers.

Objective:To seek any differential effect of combining repeated transcranial magnetic stimulation (rTMS) with a modified version of constraint-induced movement therapy (mCIMT) on the walking ability of stroke survivors.Methods:Seventy-five stroke survivors were randomly divided into a sham rTMS group, an rTMS group and a combined group, each of 25. In addition to 40 minutes of routine rehabilitation daily, including balance training, transfer training, muscle strength training, and proprioceptive training five times a week for 4 weeks, the sham rTMS group and rTMS group received sham or genuine rTMS. The combined group received 20 minutes of rTMS followed by mCIMT training 30 minutes later. The treatment was performed once a day, 5 days a week for 4 weeks. Before and after the treatment, all groups were evaluated using the Fugl-Meyer lower extremity assessment, the Berg balance scale, a 10-metre walk test and the modified Barthel index.Results:Significant improvement was observed in the average scores of all three groups in all of the assessments. The combined group′s averages were, however, significantly better than those of the other two groups.Conclusion:Supplementing mCIMT with rTMS can better improve the walking and other abilities in the activities of daily living of stroke survivors.

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

In recent years, immune checkpoint inhibitors (ICIs) have greatly improved the survival rate of non-small cell lung cancer (NSCLC) patients without driver mutation. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations have greater heterogeneity in immune microenvironment characteristics such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB). Whether ICIs is suitable for NSCLC patients with EGFR mutation has been controversial. Clinical studies have shown that immunomonotherapy has no significant effect on patients with EGFR mutant NSCLC. ICIs combined with chemotherapy and antiangiogenic drugs show good survival benefits. This paper overviews the clinical research and related mechanism of ICIs single drug or combination therapy inadvanced NSCLC patients with EGFR mutation.
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B7-H1 Antigen/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/metabolism* ; Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Ligands ; Lung Neoplasms/pathology* ; Mutation ; Tumor Microenvironment

【Objective】 To explore the recruitment and retention strategy of blood donors by investigating the age composition of blood donors in some areas of China, so as to promote blood donation and enhance clinical blood supply. 【Methods】 Through the working platform of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions, the average age and age composition of blood donors from 22 blood centers were collected, and statistical analysis was conducted after eliminating invalid data. 【Results】 The median average age of blood donors during the survey year was 30.02.The median age in 2.89% of the blood centers was lower than 25. The average age of different genders was statistically significant only in 2018(P<0.05). Fot first-time blood donors, the median constituent ratio of donors <25 and ≥25 years old was 54.53% and 44.28%, with median retention rate at 10.30% and 9.61%, respectively. The median overall participation rate of blood donors was 2.7%, with median participation rate of blood donors <25 years old at 5.1%. 【Conclusion】 The recruitment and retention of blood donor is crucial to enhance clinical blood supply. Blood donors <25 years old, with a longer period for future donation, should be the main target of blood donation recruitment. Meanwhile, the revision of upper age limit for blood donation is another important initiative to grow the blood donor pool.

In the past 20 years, with the development of molecular biology, the treatment of non-small cell lung cancer (NSCLC) has been developing. Targeted therapy has improved the survival period of patients with positive mutation of tumor driver gene. More and more targets have been found gradually. Drugs targeting different driving genes have brought the treatment of NSCLC into a promising target era. Among the many driving genes of NSCLC, the fusion of transfection proto oncogene (RET) is the addition of the epidermal growth factor receptor (EGFR), analytic lymphama kinase (ALK) and c-ros oncogene 1-receptor tyrosine kinase (ROS1) are emerging targets. Targeted drugs for RET gene fusion have been constantly updated. Recently, new high selective RET inhibitors blu-667 and loxo-292 have made important breakthroughs. This paper will review the review of the fusion mutation of RET gene in NSCLC, the detection methods, clinicopathological characteristics, targeted treatment and the research progress after drug resistance.
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