Congenital myasthenic syndrome（CMS）is a group of neuromuscular transmission disorders caused by genetic defects，and it is characterized by an early age of onset，fatigable weakness of skeletal muscle，and a high disability rate，with respiratory failure as a common cause of death. Endplate acetylcholinesterase deficiency（EAD）caused by COLQ gene mutations is a subtype of CMS，and repetitive compound muscle action potential（R-CMAP）in nerve conduction examination is the key evidence for diagnosis. The heterogeneity of clinical phenotypes of CMS often leads to misdiagnosis or missed diagnosis，resulting in delayed treatment. This article reports a case of CMS caused by COLQ mutation and summarizes the pathogenesis，mechanisms，clinical manifestations，electrophysiological characteristics，differential diagnosis，treatment，and prognosis of the disease with reference to relevant literature，in order to improve the understanding of this subtype of CMS among clinicians.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

Objective To investigate the sleep disorders and its effects on the changes in quality of life in patients with liver cancer from the hospital admission to 6 months after surgery and to analyse the correlation between the sleep disorder and quality of life.Methods A total of 214 patients who underwent surgery for liver cancer for the first time were included in the study.Demographic questionnaire,Pittsburgh sleep quality index(PSQI),and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)were used for the investigation at admission and at 1,3 and 6 months after surgery.Multiple linear regression was employed to analyse the correlation between the sleep disorders at the admission and its effect on quality of life up to 6 months after surgery.Results Toally 214 patients finished the study at admission and 209 finished the study 1 month after surgery,and 208 finished the stuoly 3 months after surgery,and 205 patients finished the study 6 months after surgery.The scores of both of PSQI at admission and the quality of life at 6 months after surgery varied across the tested time points with a statistically significant difference(both P<0.001).The overall level of sleep disorder in the patients showed a characteristic pattern with initially increasing and then decreasing,and the quality of life presented a characteristic tendency of starting from high to low and then gradually increasing.It showed that the sleep disorder at admission was attributive to the poorer quality of life at 6 months after surgery.The hierarchical regression analysis showed that among the patients at BCLC Stage A,sleep disorder at admission was the influencing factor of the quality of life at 6 months after surgery.Conclusions The sleep disorder and quality of life in the patients who had surgical operations for hepatocellular carcinoma both changed dynamically from admission to the 6 months after surgery.The quality of life was poor in the patients with sleep disorder at admission.Therefore,medical staff should enhance the sleep management at admission,conduct dynamic assessment of the sleep disorder and quality of life of the patients,and then develop continuity nursing measures to improve the quality of life after surgery.

Objective Exploring the relationship between changes in serum Golgi apparatus transmem-brane glycoprotein 73(GP73)and chitosanase 3-like protein 1(CHI3L1)levels and liver fibrosis and lesion sever-ity in patients with hepatitis B(CHB).Methods Using a case-control study,80 patients diagnosed with CHB infection and developing liver fibrosis in the Infectious Disease Department of Changsha First Hospital from June 2020 to June 2023 were selected as the liver fibrosis group,while 120 patients diagnosed with CHB infection but not developing liver fibrosis in the Infectious Disease Department of our hospital were selected as the control group.The serum GP3,CHI3L1,liver function,and fibrosis indicators of the two groups of patients were compared,and the liver fibrosis group was divided into mild according to Scheuer system standards Perform stratified analysis on patients with significant liver fibrosis.Results The serum GP3 and CHI3L1 levels in the liver fibrosis group were significantly higher than those in the control group,with statistical significance(P＜0.05);The ROC curves were plotted using serum GP3,CHI3L1,and GP3+CHI3L1,respectively.The sensitivity for diagnosing liver fibrosis in CHB patients was 62.81%,60.94%,and 96.33%,with specificity of 80.66%,80.05%,and 75.30%.The AUC values under the curves were 0.792,0.756,and 0.908,respectively;The levels of ALT,AST,HA,LN,PC III NP,C IV,and CG in the liver fibrosis group were higher than those in the control group,and the PLT measurement values were lower than those in the control group,with statistical significance(P＜0.05);49 patients with moderate to severe liver fibrosis(33 in S2 phase and 16 in S3 phase)and 31 patients with mild liver fibrosis(all in S1 phase)had significantly higher serum GP3 and CHI3L1 levels than mild patients,with statistical significance(P＜0.05);The levels of DBIL,ALT,AST,HA,LN,PC III NP,C IV,and CG in patients with moderate to severe liver fibrosis were higher than those in the mild group,and the PLT measurement values were lower than those in the mild group,with statistical significance(P＜0.05).Conclusion The serum GP3 and CHI3L1 levels in CHB patients with liver fibrosis are significantly elevated,and there is a certain correlation with the degree of liver fibro-sis.The combination of these two indicators is beneficial for diagnosing liver fibrosis in CHB patients.

Objective To establish a noninvasive diagnostic model for liver fibrosis in chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and an age of≤30 years by selecting specific indicators from the commonly used noninvasive indicators such as clinical,biochemical,and imaging indicators,to avoid invasive liver biopsy in such patients to some extent,and to guide the timing of antiviral therapy.Methods A total of 251 CHB patients with normal ALT and an age of≤30 years who underwent liver biopsy in Shenzhen Third People's Hospital and The First Hospital of Changsha from January 2019 to January 2022 were enrolled,with 175 patients in the model group and 76 patients in the validation group,and commonly used clinical indicators were obtained based on clinical experience and related articles.The two-independent-samples t test or the two-independent-samples Mann-Whitney U rank sum test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.A Spearman rank correlation analysis was used to investigate the correlation between each indicator and liver fibrosis and identify the indicators with correlation(P<0.01,r>0.200);a Logistic regression analysis was used to establish a noninvasive diagnostic model,and the receiver operating characteristic(ROC)curve was used to evaluate its performance and perform validation of the model;this model was then compared with the widely used models of aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB-4).The Kappa consistency test was used to investigate the consistency of pathological results.Results A total of 17 commonly used clinical indicators were obtained,among which 9 indicators(ALT,aspartate aminotransferase[AST],gamma-glutamyl transpeptidase[GGT],ferritin[FERR],platelet count[PLT],procollagen type Ⅲ amino-terminal peptide[PⅢP],collagen Ⅳ[CⅣ],HBV DNA,and spleen thickness)were correlated with liver fibrosis(P<0.01,r>0.232).Based on the above indicators,the predictive model was established as P=1/(1+e-γ),γ=-1.902+0.106×AST-0.011×PLT-0.265×HBV DNA+0.059×PⅢP,in which P was the probability for predicting≥S2 liver fibrosis and γ was the predictive index.The comparison between each indicator and the model showed that the model had the largest area under the ROC curve of 0.852,with a sensitivity of 92.7%and a specificity of 76.9%.The model was validated in 76 patients and showed an accuracy of 77.600%.The model was compared with APRI and FIB-4,and the results showed that the model has good accuracy.Conclusion Compared with the models of APRI and FIB-4 commonly used in the world,this model can more accurately judge the degree of liver fibrosis in such patients,thereby replacing liver biopsy to some extent and guiding the timing of antiviral therapy.

Objective:To explore the utility of combining repeated transcranial magnetic stimulation (rTMS) with action observation therapy (AOT) in improving the upper limb motor functioning of children with hemiplegic spastic cerebral palsy (HSCP).Methods:A total of 66 children with HSCP were randomly divided into a sham stimulation group, an rTMS group and a combination group, each of 22. In addition to routine rehabilitation, the sham stimulation and rTMS groups received the relevant treatment or sham treatment, while the combination group also received action observation therapy (AOT). The treatment was administered daily, five times a week for 12 weeks. Before and after the treatment, everyone′s upper limb muscle tone was evaluated using the modified Ashworth Scale (MAS), and fine motor function, grasping and hand coordination were quantified using the fine component of the Peabody Motor Development Scale (PDMS-FM) and the Carroll upper limb function test (UEFT).Results:After the treatment, significant improvement was documented in the average MAS scores of the bicipital arm and wrist flexors of all three groups, and also in their average PDMS-FM scores, fine motor quotient (FMQ) scores and UEFT scores. After 12 weeks the combination group significantly out-scored the other two groups in terms of their average biceps and wrist flexor MAS scores, PDMS-FM grasping area and visual-motor integration area scores, FMQ score and UEFT score. There was no significant difference between the other two groups in any of the outcome measurements, on average.Conclusions:Supplementing rTMS and routine rehabilitation with AOT more effectively improves the upper limb muscle tension, upper limb functioning and fine finger manipulation of children with hemiplegic spastic cerebral palsy.

Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

Humans ; Asthma/drug therapy* ; Biological Therapy