Purpose To detect the expression of PP1A and GSDME and the abundance of CD8+T lymphocytes in colorectal cancer,and to explore the correlation and clinical significance of PP1A and GSDME mediated pyroptosis.Methods GEPIA da-tabase was applied to analyze the mRNA expression of PP1A and GSDME in colorectal cancer and normal tissues.Western blot assay was used to detect the expression of PP1A in colorectal cancer and the corresponding normal mucosa.Immunohisto-chemistry was applied to detect the expression of PP1A and GS-DME and CD8+T lymphocytes abundance in 107 colorectal car-cinomas and normal mucosa adjacent to the carcinomas.Spearman rank correlation was used to analyze the correlation between PP1A,GSDME and CD8+T cells abundance.Results The GEPIA database search showed that mRNA expression of PP1A and GSDME in colorectal cancer differed compared to normal tissues(P＜0.05).Western blot analysis showed that the relative expression of PP1A in colorectal cancer tissue was significantly higher than that in para-cancerous tissues(0.937 vs 0.643,P＜0.001).Immunohistochemical results showed that the expression of PP1A in colorectal cancer tissues was signifi-cantly higher than that in normal mucosa(P＜0.05).The ex-pression of GSDME in cancer tissue was closely correlated with patients'age,clinical stage and mismatch repair proteins(P＜0.05),and the distribution of CD8+T cells in the cancer infil-tration front was significantly higher than that in the normal mu-cosa,and the distribution of CD8+T cells in the cancer was cor-related with pT stage,clinical stage and lymph node metastasis.Spearman correlation analysis showed that PP1A was negatively correlated with GSDME expression(r=-0.196,P＜0.05).The overall survival PP1A-positive colorectal cancer patients was worse than that of PP1A-negative patients(P＜0.05),and the prognosis of patients was correlated with the degree of differentia-tion,lymph node metastasis,pT stage and clinical stage.Posi-tive expression of PP1A,degree of differentiation,clinical stage,pT stage and lymph node metastasis are independent risk factors affecting the prognosis of colorectal cancer patients.Conclusion PP1A is highly expressed in colorectal cancer and negatively correlated with GSDME-mediated cell pyroptosis,and the differ-ential expression of both is closely related to the progression and prognosis of colorectal cancer,which can be used as a potential indicator for judgment of the prognosis of colorectal cancer pa-tients.The differential distribution of CD8+T cells may be asso-ciated with GSDME-mediated cell pyroptosis and tumor develop-ment.

Objective To explore and optimize the in vitro primary culture method of astrocytes in neonatal mouse cerebral cortex, which provides a better solution for the in vitro culture of astrocytes.Methods In order to opti-mize the in vitro culture method of mouse cerebral cortex astrocytes, 3-day-old C57BL/6J mouse cerebral cortex tis-sues were taken, meninges and blood vessels were removed, digested by pancreatic enzymes and centrifuged, and high-glucose dulbecco's modified eagle medium (DMEM) was added to form cell suspension, which was purified by differential adhesion method, cross hand method and constant temperature shaking method.The cells were inoc-ulated in poly-D-lysine-coated culture bottles with different culture densities, and the purity of astrocytes was deter-mined by morphological observation and immunofluorescence staining.Results The cells were inoculated at a den-sity of 5 × 106 cells per bottle with good effect and high activity.The purity of astrocytes reached 99％ by using high sugar DMEM medium combined with differential adhesion method, cross hand method and constant temperature shaking method.Conclusion The primary culture method of astrocytes in mouse cerebral cortex is successfully es-tablished and optimized.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Background: The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. Objectives: This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. Methods: AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. Results: Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. Conclusions These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.

Objective:To investigate the body composition and sarcopenia in patients with stable chronic obstructive pulmonary disease (COPD) and to analyze the influencing factors.Methods:A total of 220 patients with stable COPD were enrolled in the study from China-Japan Friendship Hospital during July 2018 to December 2019; 220 age and sex-matched healthy subjects (control group 1) and 220 healthy young adults aged 20-40 years (control group 2) were enrolled from the community. The body composition was measured by bioelectrical impedance method. The demographic characteristics, disease conditions, living background and other related factors were collected by questionnaire. T test or one-way ANOVA were used for comparison between groups, and non parametric test was used for non normal distribution data.Results:Compared with the control group 1 and control group 2, the body fat rate ( Z=-10.037, t=-8.411), the fat free mass index ( Z=-8.165, t=-7.856), and appendicular skeletal muscle index (ASMI) ( t=-7.158, t=-11.989) were significantly lower in stable COPD patients ( P<0.05). Among 220 patients with stable COPD, 51 (23.2%) were diagnosed as sarcopenia; the prevalence of sarcopenia was 18.3% (24/131) in men and 30.3% (27/89) in women (χ2=4.297, P=0.038). The decreased ASMI and grip strength in COPD patients with sarcopenia were significantly associated with age≥75 (χ2= 15.746, F= 14.048), female sex ( Z=5.805, t=2.672), low income ( Z=-4.291, t=-4.789), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade Ⅳ (χ2=22.644, F=3.905), Modified British Medical Research Council (mMRC) Dyspnea Scale grade 4 (χ2=12.475, F=4.369), not receiving systematic health education ( Z=-4.239, Z=-2.474), no exercise (χ2=14.786, F=3.402), insufficient nutrition intake (χ2=40.531, F=10.529). The range of 6-min walking distance was (110-268) m, that was even shorter for patients with mMRC dyspnea scale grade 4 ( F=3.468, P<0.05). Conclusion:The impairment of body composition is common in COPD patients, which will further affect the body function. It is suggested that the routine evaluation of COPD should include the measurement of body composition.

Background: The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. Objectives: This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. Methods: AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. Results: Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. Conclusions These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.

To investigate the effects of ()infection on autonomic nervous function and calcitonin gene-related peptide in patients with functional dyspepsia(FD). Thirty-one patients with FD matching Rome Ⅳ criteria were included and divided into -positive group and -negative group.All patients were evaluated by Symptom Index of Dyspepsia(SID),Nepean Dyspepsia Index(NDI),and Hospital Anxiety and Depression Scale(HADS).Their heart rate variability(HRV)and calcitonin gene-related peptide(CGRP)level were also measured. There were no significant differences in SID(=-0.858, =0.858),NDI(=-1.464, =0.143),and Hospital Depression Scale score(=0.699, =0.485).However,the Hospital Anxiety Scale score was significantly higher in -positive group than the -negative group(=-2.470, =0.014).The level of CGRP in -positive group[(0.999±0.274)ng/ml]was significantly higher than that in the -negative group[(0.812±0.172)ng/ml;=2.238, =0.033].HRV data showed no significant difference between these two groups at very low frequency(=-1.210, =0.236),low frequency(LF)(=0.419, =0.678),high frequency(HF)(=0.612, =0.546),LF/HF(=-0.882, =0.399),and total power(=-0.963, =0.344). In FD patients,patients with -positive FD patients have higher depression and CGRP levels than those without infection,although their dyspepsia symptoms and HRV show no notable changes.
Anxiety ; Calcitonin ; Calcitonin Gene-Related Peptide ; Dyspepsia ; Helicobacter Infections ; Helicobacter pylori ; Humans

OBJECTIVE: To explore the genetic basis for a patient with episodic ataxia and pyramidal tract signs. METHODS: The patient was subjected to high-throughput sequencing, Sanger sequencing and analysis of dynamic variant site associated with spinocerebellar ataxias (SCA). RESULTS: The patient was an adolescent male presenting with episodic ataxia, bilateral knee hyper-reflexia and ankle clonus. By genetic testing, he was found to harbor a c.1159-1162dupAAGT variant of PDHA1 gene. The same variant was not found in his parents and elder sister. No abnormalities were found by SCA dynamic variant screening. The patient was diagnosed as pyruvate dehydrogenase E1alpha deficiency due to variant of the PDHA1 gene. CONCLUSION The de novo c.1159-1162dupAAGT variant of the PDHA1 gene probably underlies the disease in the proband. Patients with pyruvate dehydrogenase E1alpha deficiency have complex phenotypes and very few have pyramidal tract involvement, which may be attributed to abnormal early neuronal development.

Objective:To investigate the distribution and influencing factors of the ocular biological parameters related to refractive development in school-age children.Methods:A cross-sectional study was performed.A total of 1 091 children aged 6-12 years old from July, 2017 to August, 2018, resident in downtown of Zhenjiang were enrolled in this study.The corneal radius of curvature (CR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated after AL and corneal curvature (K) were measured by IOL Master.After pupillary dilatation with 0.5% tropicamide, cycloplegic retinoscopy was performed to identify refractive status.According to the spherical equivalent refraction (SER), all right eyes were classified into myopia, hyperopia and emmetropia.The comparison of the above parameters between different genders, as well as among different age groups and different refractive status groups were determined while the relative factors of the biological parameters and refractive status were analyzed by multivariate regression analysis.The study protocol was approved by the Ethics Committee of Affiliated People's Hospital of Jiangsu University (No.K-20190153-W).Results:There were statistical differences in AL, SER and AL/CR value among different age groups ( F=32.34, P<0.01; F=33.69, P<0.01; F=2.19, P=0.04), which showed that refractive status shifted to myopia as well as AL and AL/CR value were increased with age.Compared with the girls, the boys had significantly longer AL, greater CR, greater AL/CR value, and smaller K ( t=7.58, P<0.01; t=-7.48, P<0.01; t=-8.08, P<0.01; t=-2.14, P=0.03). There were statistical differences in AL and AL/CR value among different refractive status groups ( F=192.68, P<0.01; F=143.15, P<0.01). The myopia group had longer AL and greater AL/CR value than the other two groups.Children whose parents were not myopic and children who had outdoor activities more than 14 hours per week and did homework less than 20 hours per week and children who slept more than 9 hours per day had shorter AL, smaller AL/CR value, and were more inclined to hyperopia or emmetropia.The results of multivariate regression analysis suggested that children aged from 6-12 years old with older age, female, increased height, parental myopia, and more time in homework or less time in outdoor activities per week may be more likely to have myopia, and longer AL or bigger AL/CR value was correlated with older age, male, greater body mass index (BMI), increased height, myopia conditions of parents, more time of doing homework, and less time in outdoor activities. Conclusions:The SER shifts to myopia with age in 6 to 12-year-old school-age children in the downtown of Zhenjiang.And there are significant differences in AL, CR and AL/CR value between boys and girls.Female, older age, increased height, more time in homework, less time in outdoor activities, and parental myopia are associated with more negative SER.

Objective:To investigate the correlations of dynamic iodine nutrition status and thyroid function in pregnant women and newborns in Lingang of Shanghai, so as to provide an evidence for whether urine iodine testing and iodine supplementation should be carried out.Methods:A prospective study was conducted by randomly selecting pregnant women from October 2017 to October 2018 in Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health Sciences. The pregnant women were divided into early (5-12 weeks), middle (22-24 weeks), late pregnancy (36-37 weeks). Samples of serum and 24 hours urine were collected to test on thyrotropin (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroid peroxidase (TPOAb), anti-thyroglobulin (TgAb) and urinary iodine. TSH in neonatal heel blood was analyzed 72 h after birth (newborns from pregnant women in the late pregnancy). The differences of thyroid function of pregnant women with different pregnant periods and different urinary iodine levels were analyzed, as well as the neonatal TSH levels of pregnant women with different urinary iodine levels. Results:A total of 109, 90 and 54 cases of pregnant women in early, middle and late pregnancy were investigated and the medians of urinary iodine were 120.95, 136.30 and 116.80 μg/L, respectively. There was no significant difference in urinary iodine content among different pregnant periods( P > 0.05). The proportions of urinary iodine level less than 150 μg/L in early, middle and late pregnancy were 75.2% (82/109), 61.1% (55/90) and 59.3% (32/54), respectively. The median values of serum TSH in early, middle and late pregnancy were 1.81, 1.95 and 2.29 mU/L, mean values of FT 3 were (5.21 ± 0.84), (4.79 ± 0.72) and (4.13 ± 0.56)pmol/L, and means of FT 4 were (16.48 ± 2.58), (15.02 ± 2.78) and (13.31 ± 1.87) pmol/L, respectively. The FT 3 and FT 4 levels in the late pregnancy were lower than those in the early and middle pregnancy, while the TSH levels in the late pregnancy were higher than those in the early and middle pregnancy. There were no significant difference in serum FT 3, FT 4 and TSH levels among early, middle and late pregnancy under different urinary iodine levels. The median TSH of newborn heel blood was 1.48 mU/L. There was no statistically significant difference between the neonatal heel blood TSH level of pregnant women with urinary iodine < 150 μg/L [1.45(1.09, 2.23)mU/L] in late pregnancy and those with urinary iodine ≥150 μg/L [1.42 (1.14, 2.61) mU/L, Z=- 0.354, P > 0.05]. Conclusions:There is mild iodine deficiency in pregnant women in Lingang of Shanghai. However, due to the compensatory regulation, it has no significant effect on the thyroid function of mother and newborn. Monitoring of iodine nutrition of pregnant women should be carried out and iodine supplementation should be done scientifically and reasonably.