Objective:To analyze the clinical characteristics, imaging, myopathology and outcomes of patients with COVID-19 related autoimmune myopathy.Methods:The clinical features, serum creatine kinase (CK), myositis antibodies, muscle magnetic resonance imaging, myopathology and therapy of 5 patients with COVID-19 related autoimmune myopathy diagnosed in Peking University First Hospital from December 2022 to April 2023 were collected. The effects of the therapy after a short term follow up were analyzed.Results:Among the 5 patients, there were 3 males and 2 females, with onset age of 42-86 years. All patients presented with proximal muscle weakness in the recovery term of COVID-19. Myalgia was noted in 3 cases, dysphagia in 1, skin damage in 2, interstitial lung disease in 1. The serum CK of the 5 patients was 1 663-16 000 IU/L, 1 patient had anti-3-hydroxy-3-methylglutaryl-CoA reductase autoantibodies and 1 patient had anti-signal recognition particle autoantibodies. The electromyography showed myogenic lesions in all patients. Muscle magnetic resonance imaging showed diffuse muscle edema in all patients, myofascial edema in 3 and subcutaneous-tissue edema in 3. The muscle biopsies in 4 patients revealed necrotic myopathy,with high P62 expression in muscle fibers. The electromicroscopy of 2 patients revealed vacuolated mitochondria and intranuclear tubulofilamentous inclusions in muscle fibers. Four patients were treated with glucocorticoids, of whom 2 patients combined with intravenous immunoglobulin, tacrolimus or cyclophosphamide. One case had close monitoring without drug therapy. They showed significant improvement, but the CK was still abnormal in 4 patients.Conclusions:COVID-19 leads to immune mediated myopathy. The manifestation of patients is characterized by proximal predominant weakness and high creatine kinase level. Muscle magnetic resonance imaging shows diffuse muscle edema. The muscle biopsies reveal necrotic myopathy. The effectiveness of immunosuppression needs to be further studied.

ObjectiveTo explore the effect of exposure to atmospheric particulate matters on the outpatient visits of respiratory disorders in Jiaxing City，Zhejiang Province. MethodsDaily air pollutant monitoring data，meteorological data and outpatient visits of respiratory disorders in Jiaxing City from 2019 to 2021 were collected．A generalized additive model was applied to evaluate the effect and laggeel effect of the concentrations of atmospheric particulates for outpatient visits of respiratory disorders after adjusting for secular trend， day-of-the-week effect， holiday effect， and meteorological variables. ResultsThe daily average concentrations of PM_2.5， PM₁₀， O₃ and NO₂ exceeded the standard， and the proportion of days exceeding the standard was 3.4%， 1.3%， 11.0% and 0.8%， respectively. Every 10 μg·m^-3 increase in PM_2.5 concentration showed the strongest effects on the daily outpatient visits of respiratory disorders， adult and childhood respiratory disorders all on lag07 with ER（95%CI） being 2.29%（1.35%‒3.24%）， 2.31% （1.39%‒3.23%） and 2.65 % （1.36%‒3.96%）， respectively. The maximum ER of outpatient visits for respiratory disorders in children was higher than that in adults. Every 10 μg·m^-3 increase in PM₁₀ concentration showed the strongest effects on the daily outpatient visits of respiratory disorders on lag07， adult respiratory disorders on lag06 and childhood respiratory disorders on lag07 with ER（95%CI） being 1.42% （0.87%‒1.96%）， 1.49%（0.99%‒1.99%） and 1.61% （0.87%‒2.36%）， respectively. The results of double-pollutant model showed that the effect of atmospheric particulate reduced after O₃ was introduced into the model. ConclusionThere are a short-term effect and a laggeel effect of atmospheric particulate on the outpatient visits of respiratory disorders. It is necessary to strengthen the health protection of the respiratory system of the population， especially the children.

Objective:To explore the safety and effectiveness of medium-frequency electrotherapy for increasing the volume of the latissimus dorsi muscle.Methods:Fifteen adult New Zealand white rabbits were randomly divided into three groups, namely group A, group B, and group C, with 5 rabbits in each group. This was a self-control study, with the right latissimus dorsi muscle as the experimental group and the left latissimus dorsi muscle as the control group. The three groups corresponded to three different current intensity levels: 7.062 mA for group A (6th gear), 10.593 mA for group B (9th gear), and 14.124 mA for group C (12th gear). After the 12th, 24th, and 36th sessions of the experiment, ultrasonography was used to collect the thickness of the latissimus dorsi muscle. After the 36th electrostimulation, the latissimus dorsi muscle samples were collected to measure their in vivo muscle thickness and wet weight and were then sent for HE and MASSON staining.Results:After the 12th, 24th, and 36th electrostimulation sessions, ultrasonographic sampling in groups A and B showed an increase in the thickness of the right latissimus dorsi muscle compared to the left; for example, the thickness on the right of group B increased by 37.8%. The wet weight data collected after the 36th electrostimulation in groups A and B showed an increase in the right latissimus dorsi muscle compared to the left; for example, the wet weight on the right of group B increased by 5.04%.Conclusions:Different electrostimulation modes of medium-frequency therapy technology can induce muscle fiber thickening or atrophy. In this experiment, the 9th gear (10.593 mA) of medium-frequency therapy technology may be a suitable choice for inducing muscle fiber thickening, and the 12th gear (14.124 mA) may be a suitable choice for inducing skeletal muscle thinning.

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

Objective:To determine the clinical, pathological and imaging phenotypes of pediatric patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy to explore its diagnostic strategies.Methods:The clinical features of 10 pediatric patients with anti-HMGCR myopathy in the Department of Neurology, Peking University First Hospital from July 2014 to July 2021 were collected. Muscle biopsies were performed in all patients, with histological, enzymatic histochemical and immunohistochemical staining.Results:The male to female ratio was 6∶4, the age of onset was 3-16 (8.3±3.7) years, 2 cases had subacute onset, and 8 cases experienced chronic progressive onset. All patients presented with neck and proximal muscular weakness of all limbs. Skin rash was observed in 2 cases. Serum creatine kinase was 998-27 981 U/L. The electromyography results were available from 6 cases, who experienced myogenic changes. The muscle magnetic resonance imaging was performed in 5 cases and revealed muscle edema predominantly in posterior compartment of thigh, with mild fatty infiltrate in 2 cases. An initial diagnosis was limb-girdle muscular dystrophy in 7 cases, but with subsequently negative genetic testing. Muscle biopsies revealed scattered necrotic fibers and regenerating fibers, complement deposition in sarcolemma basement-membrane areas of non-necrotic fibers and a few of lymphocyte infiltrate in all specimens. Moreover, a high frequency of major histocompatibility complex Ⅰ expression in muscle fibers was observed in 9 cases, proliferation of connective tissue of endomysium in 8 cases, muscle fiber hypertrophy in 4 cases and vacuoles in 2 cases.Conclusions:Pediatric anti-HMGCR myopathy is frequently misdiagnosed as muscular dystrophy. Systematic consideration of anti-HMGCR myopathy and testing for myositis specific antibody in children with genetically unconfirmed muscular dystrophy may help the differential diagnosis.

To explore the different chloroplast genome characteristics of Sinopodophyllum hexandrum, five chloroplast genome sequences of S. hexandrum were compared. Its genome map, repeat sequence, codon preference, inverted repeat (IR)/single-copy (SC) boundary, alignment of chloroplast genome sequences and phylogenetic were analyzed using bioinformatics tools. The results showed that: the total length of five chloroplast genomes of S. hexandrum, with a typical tetrad structure, were 157 203-157 940 bp, and a total of 133-137 genes were annotated, reflecting the diversity of chloroplast genomes of S. hexandrum. Different chloroplast genomes of S. hexandrum has different simple sequence repeat (SSR), where simple repeat of single nucleotide of A/T were the majority among the SSR detected. The interspersed repetitive sequences included direct, palindromic and inverted repeats. The value of effective number of codon (ENc) which was analyzed by using codon bias was 51.14~51.17, the proportion of GC and GC3s was less than 50%, the codon usage pattern tended towards frequently use of A/U-ending bases. Genome sequences and the IR/SC boundaries of five chloroplast genomes of S. hexandrum were relatively conservative. Phylogenetic analysis showed that S. hexandrum and Podophyllum pettatum had the closest genetic relationship. In summary, the chloroplast genome characteristics and evolutionary relationship of different chloroplast genomes of S. hexandrum were obtained, which may facilitate the utilization, protection, variety identification and genetic evolution of S. hexandrum resources.
Phylogeny ; Genome, Chloroplast ; Chloroplasts/genetics* ; Genomics ; Evolution, Molecular

Objective:To explore the eye movement characteristics of social cognitive processing in schizophrenia patients across different stages and its association with clinical symptoms.Methods:Fifteen patients with first-episode schizophrenia, forty-six patients with chronic inpatient schizophrenia, thirty-six patients with psychiatric clinical high-risk syndrome, and twenty-six healthy controls were recorded using eye tracking technology when viewing social interaction pictures. Covariance analysis and partial correlation analysis were conducted by SPSS17.0.Results:When watching the pictures of person communication, there were statistically significant differences in the average fixation duration of the four groups of subjects ((294.6±36.7)ms in control group, (280.0±54.0)ms in clinical high-risk group, (268.5±34.9)ms in first-episode group, and (315.7±75.7) ms in chronic group, respectively, F=3.18, P=0.027). When viewing the pictures of no person landscape, the average saccade amplitude of the four groups of subjects was significantly different (5.3±1.1) ° in control group, (4.7±1.1) ° in clinical high-risk group, (5.2±1.0) ° in first-episode group, and (4.4±1.2) ° in chronic group, respectively, F=3.37, P=0.021). The average fixation duration of chronic patients when observing person communication pictures was positively correlated with the total score of PANSS (partial correlation coefficient=0.313, P=0.039). The average fixation duration of chronic patients when observing the other two types of pictures were also positively correlated with the total score of PANSS (partial correlation coefficient=0.320, P=0.034, no person communication pictures; partial correlation coefficient=0.372, P=0.013, no person landscape pictures) . The average fixation duration of chronic patients when observing pictures of no person landscape was positively correlated with the PANSS positive symptom score (partial correlation coefficient=0.321, P=0.034). The average fixation duration of chronic patients when observing any type of picture was positively correlated with the PANSS general symptom score (person communication pictures: partial correlation coefficient=0.385, P=0.010; no person communication pictures: partial correlation coefficient=0.409, P=0.006; no person landscape pictures: partial correlation coefficient=0.465, P=0.001). In the first-episode patient, the average saccade amplitude when observing no person communication pictures was positively correlated with the PANSS positive symptom score (partial correlation coefficient=0.555, P=0.049). In the clinical high-risk group, the average saccade amplitude when observing person communication pictures was negatively correlated with the SOPS positive symptom score (partial correlation coefficient=-0.373, P=0.030). Conclusion:There are statistically significant differences of eye movement characteristics of social cognitive processing in patients with schizophrenia across different clinical stages.The average saccade amplitude is more sensitive than the average fixation duration in predicting the severity of symptoms in clinical high-risk patients.

More and more therapeutic monoclonal antibodies(mAbs)are widely used for treating various illnesses such as cancer and autoimmune diseases due to the specific and efficient properties of mAbs.All of the currently licensed therapeutic mAbs are of the IgG class.Fc region of IgG has a N-glycan which is structural heterogeneity.The glycan on Fc region has many significant roles on the structure,the effector functions and pharmacokinetics of mAbs.The glycan of Fc region can be changed through genome editing and optimization of cell culture condition.This review presents an overview of the role of the various glycans in the effector functions of therapeutic mAbs and the impact of various parameters on glycosylation pattern of therapeutic mAbs.

Objective To learn the change of causes sequences, the pattern and dynamic trend of causes of death for the inhabitants in Jiaxing from 2009 to 2014, and to provide a major reference for health decisions and disease control and prevention. Method This study was based on chronic disease surveillance information management data in Zhejiang province from 2009 to 2014. ICD-10 criteria and method was used to classify the causes of death. To evaluate health status of those residents, the relative health indicators such as mortality rate, constituent ratio, PYLL, AYLL, PYLL‰were used. Results The average mortality rate of residents was 691.92/100 000 of Jiaxing from 2009 to 2014, with male 760.73/100 000 and female 624.64/100 000 (the average mortality rate of male was significantly higher than that of female, χ2=455.52, P<0.01). The top five causes of death of local residents were malignant neoplasm, respiratory system diseases, cerebrovascular diseases, injury and poisoning, heart diseases, which accounted for 87.95%of all deaths. The mortality caused by malignant neoplasm was 189.53/100 000, which accounted for 31.90% of five main death causes (the rate of male was significantly higher than that of female, χ2=3767.70, P<0.01). The PYLL of malignant neoplasm were 38 368 years, which was the main reason. The AYLL of injury and poisoning were 9.58 years. Conclusion The average mortality rate of residents has been declining across the Jiaxing, but the mortality rate of malignant neoplasm is increasing year by year. The data suggested that malignant neoplasm, cardiovascular disease, unintentional falls, motor vehicle traffic accidents and pneumonia are major factors affecting the health of the population.

Objective To study effect of Taxol on protein O-GlcNAcylation levels and investigate whether protein O-GlcNAcylation levels can affect the sensitivity of breast cancer cells to Taxol.Methods Western blot analysis was performed to examine protein O-GlcNAcylation levels and the expression of enzymes related to O-GlcNAcylation biosynthesis in Taxol treated breast cancer cells.RT-qPCR was used to analyze the effects of Taxol on OGA and OGT mRNA expression in cancer cells.The sulforhodamine B colorimetric assay was used to determine the effect of alteration of protein O-GlcNAcylation on the anti-proliferation of Taxol in breast cancer cells by adding OGA inhibitor and OGT inhibitor, respectively.Results Taxol treatment enhanced protein O-GlcNAcylation levels in dose-and time-dependent manners in breast cancer cell MDA-MB-231 ( P <0.05 ) .Taxol increased the mRNA levels of OGT and OGA after MDA-MB-231 cells were treated for 24 h(P<0.05).As OGA inhibitors increased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was increased.As OGT inhibitor decreased protein O-GlcNAcylation levels, the sensitivity of MDA-MB-231 to Taxol was reduced.Conclusion Taxol treatment can enhance protein O-GlcNAcylation levels and the changes of O-GlcNAcylation levels alter the sensitivity of breast cancer cell MDA-MB-231 to Taxol.