Objective:To analyze the mutations of globin genes among patients suspected for thalassemia from the Shanghai area.Methods:A total of 4 644 patients diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between June 2016 and December 2019 were selected as the study subjects. The patients were tested for common mutations associated with thalassemia gene by Gap-PCR and reverse dot blotting (RDB). Patients were suspected to harbor rare mutations based on the inconsistency between hematological phenotypes and results of common mutation detection, and were further analyzed by Gap-PCR and Sanger sequencing.Results:Among the 4 644 patients, 2 194 (47.24%) were found to carry common thalassemia mutations, among which 701 (15.09%) were α-thalassemia, 1 448 (31.18%) were β-thalassemia, and 45 (0.97%) were both α- and β-thalassemia. Forty six samples were found to harbor rare mutations, which included 17 α-globin gene and 29 β-globin gene mutations. CD77(CCC>ACC) ( HBA2: c. 232C>A) of the α-globin gene, NG_000007.3: g. 70567_71015del449, codon 102(-A) ( HBB: c. 308_308delA) and IVS-Ⅱ-636 (A>G) ( HBB: c. 316-215A>G) of the β-globin gene were previously unreported new types of globin gene mutations. Conclusion:Among the 4 644 patients, the detection rate for common thalassemia mutations was 47.24%, whilst 46 samples were detected with rare gene mutations. The type of gene mutation types were diverse in the Shanghai area. The study has provided more accurate results for genetic diagnosis and counseling.

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective:To investigate the effects of silicon photomutipliers (SiPM) detector and Bayesian penalized likelihood (BPL) reconstruction algorithm on semiquantitative parameters of 18F-FDG PET/CT and diagnostic efficiency for solitary pulmonary nodules/masses compared with traditional photomultiplier tube (PMT) and ordered subsets expectation maximization (OSEM). Methods:From March 2020 to January 2022, 118 patients (76 males, 42 females, age (63.0±10.1) years) newly diagnosed with solitary pulmonary nodules/masses in First Hospital of Shanxi Medical University were prospectively enrolled and underwent 18F-FDG PET/CT imaging with two different PET/CT scanners successively. The images were divided into PMT+ OSEM, SiPM+ OSEM and SiPM+ BPL groups according to PET detector and reconstruction algorithms. The SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of pulmonary nodules/masses were measured, then signal-to-noise ratio (SNR) and signal-to-background ratio (SBR) were calculated. One-way analysis of variance and Kruskal-Wallis rank sum test were performed to compare differences of above parameters among groups. ROC curve analysis was used to analyze the optimal threshold of SUV max for the differential diagnosis of pulmonary nodules/masses and AUCs were obtained. Results:There were 83 malignant nodules and 35 benign nodules. The image quality of SiPM+ BPL group (4.23±0.64) was better than that of SiPM+ OSEM group (3.57±0.50) or PMT+ OSEM group (3.58±0.51; F=54.85, P<0.001). There were significant differences in SUV max (7.57(3.86, 15.61) vs 4.95(2.22, 10.48)), SUV mean (4.43(2.28, 9.12) vs 2.84(1.21, 5.71)), MTV (3.54(1.57, 7.67) vs 5.09(2.83, 11.79)), SNR (28.12(12.55, 54.38) vs 20.16(8.29, 41.45)) and SBR (4.03(1.83, 7.75) vs 2.32(0.96, 5.03)) between SiPM+ BPL and SiPM+ OSEM groups ( H values: 16.63-37.05, all P<0.001). The optimal threshold values of SUV max in SiPM+ BPL, SiPM+ OSEM and PMT+ OSEM were 3.31, 2.21, 2.05 with AUCs of 0.686, 0.689, 0.615 for nodules < 2 cm, and were 10.29, 6.49, 4.33 with AUCs of 0.775, 0.782, 0.774 for nodules/masses ≥2 cm. Conclusions:Image quality and parameters of pulmonary nodules/masses are mainly affected by the reconstruction algorithms. BPL can improve SUV max, SUV mean, SBR and SNR, but reduce MTV without significant effect on liver parameters. SiPM+ BPL has a higher diagnostic threshold of SUV max than SiPM+ OSEM and PMT+ OSEM.

Objective:To learn about the application of medical ethics review in scientific research and prevention of endemic diseases.Methods:The method of retrospective analysis was used, original articles on field epidemiological investigation and clinical medicines published by Chinese Journal of Epidemiology from 2017 to 2020 were collected. Examination of medical ethics in national, provincial and municipal fund programs and nonfund projects was carried out. Statistical analysis was performed using Cochran-Armitage trend test and Cochran-Mantel-Haenszel (CMH) test.Results:A total of 638 articles were collected from 2017 - 2020, with 36 excluded and 602 remaining. The proportion of papers published after medical ethics review over the past four years was 56.85% (83/146), 62.50% (105/168), 59.87% (94/157), and 60.31% (79/131), respectively. There was no statistically significant difference in trend testing ( Z = 0.41, P > 0.05). There was no statistically significant difference in the proportion of papers produced by academic works, on-site investigations, and clinical medicine programs among different years (χ 2 = 0.01, 1.31, 1.92, P > 0.05). The proportion of papers published that supported by various fund programs that had undergone medical ethics review over the past four years was 60.55% (66/109), 62.28%(71/114), 62.38% (63/101), and 60.22% (56/93), respectively. The trend test showed no statistically significant difference( Z = - 0.03, P > 0.05). There was no statistically significant difference in the proportion of papers published that supported by national level projects, provincial and ministerial level projects, and municipal level projects among different years (χ 2 = 0.06, 0.02, 0.19, P > 0.05). The difference in the trend test of the output papers of research projects approved by the higher-level ethics committee and marked with approval numbers over the past 4 years was statistically significant ( Z = 2.85, P < 0.01); the difference was statistically significant when compared across years (χ 2 = 8.13, P < 0.01); the proportion of papers increased from 8.22% (12/146) in 2017 to 18.08% (25/131) in 2020 (χ 2 = 7.04, P = 0.008). There was no statistically significant difference ( Z = - 0.53, P > 0.05) in the proportion of papers that expressed their consent in terms of informed consent over the past 4 years; There was no statistically significant difference in comparison between different years (χ 2 = 0.28, P > 0.05). Conclusions:Medical ethics review has been taken seriously by the majority of researchers and is widely used in endemic scientific research and prevention projects.

Objective:To improve the quality of 18F-fluorodeoxyglucose (FDG) PET images at different acquisition times through deep learning (DL) PET image reconstruction methods. Methods:A total of 45 patients (20 males, 25 females; age (52.0±13.6) years) with malignant tumors and PET/CT scans from September 2020 to October 2020 in the Department of Nuclear Medicine of the First Hospital of Shanxi Medical University were included in this retrospective study. The short acquisition time 30 s/bed PET images from the raw list mode were selected as the input of DL model. DL image reconstruction model, based on the Unet algorithm, was trained to output imitated PET images with full dose standard acquisition time (3 min). The image quality evaluation and quantitative analysis were carried out for four groups of images: DL images, 30 s, 90 s, and 120 s images, respectively. The quality of PET images in four groups was evaluated using the five-point method. Liver background activities, lesions quantification parameters (maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)), and first-order texture features (skewness, kurtosis, uniformity, entropy) were measured. Kappa test, χ2 test and one-way analysis of variance (least significant difference t test) were used for data analysis. Results:The image quality scores between four groups were highly consistent ( Kappa=0.799, P<0.001). The number of patients with scores≥3 in DL, 30 s, 90 s and 120 s groups were 6, 4, 7 and 8, respectively ( χ2=125.47, P<0.001). The liver SD of DL group was significantly lower than that of 30 s group (0.26±0.07 vs 0.43±0.11; F=3.58, t=-7.91, P<0.05). The liver SNR of DL group was higher than that of 30 s group (11.04±4.36 vs 5.41±1.41; F=10.22, t=5.40, P<0.05). The liver SD and SNR of DL group were similar to those of 90 s group (0.39±0.16, 8.46±3.34; t values: -0.87 and 2.17, both P>0.05). In 18 tumor lesions with high uptake, SNR and CNR of DL group were significantly higher than those of 30 s group (60.21±29.26 vs 38.38±16.54, 22.26±15.85 vs 15.41±9.51; F values: 13.09 and 7.05; t values: 5.20 and 4.04, both P<0.001). There were statistically significant differences among four groups in the first-order texture features ( F values: 4.30-9.65, all P<0.05), but there was no significant difference between DL group and 120 s group ( t values: from -1.25 to 0.15, all P>0.05). Conclusion:DL reconstruction model can improve the quality of short-frame PET images, which meets the needs of clinical diagnosis, efficacy evaluation and radiomics research.

Objective:To discuss the challenges and problems of the prevention and control of emerging infectious diseases in Shanghai as a megacities.Methods:An imported case of cutaneous anthrax occurred in Shanghai on May 30, 2019. Shanghai Municipal Center for Disease Control & Prevention conducted an epidemiological investigation and treatment of the cases; after this case, the data of patients with cutaneous anthrax were collected, and an epidemiological study was conducted. Meanwhile, the wound and blood samples of the patient were collected for laboratory testing.Results:Of the seven wound samples of the patient, 6 were positive for the Bacillus anthracis nucleic acid test, and the double serological test results showed a 4-fold increase in the titer of anthrax antibodies. Shanghai CDC conducted an epidemiological investigation of the confirmed cases and observed its contacts. After treatment, the patients recovered, and no other issues appeared among the 19 contacts. Conclusions:Shanghai must strengthen the training of clinicians on emerging infectious diseases to achieve early detection, diagnosis, and treatment of imported infectious diseases and reduce the incidence, spread, and death of the diseases. At the same time, multi-department joint prevention and control are needed to prevent and control secondary cases.

In recent years, with the widespread clinical application of moxibustion, the clinical trials on moxibustion research are also increasing. However, the establishment of negative control of moxibustion, also called as mimicking moxibustion, has become a major challenge in the randomized controlled trials (RCTs) . In this review, we summarized the establishment methods of mimicking moxibustion in RCTs at home and abroad, and evaluated and elaborated the design and application methods of mimicking moxibustion models from thermal effect, light radiation effect and smoke effect that generated by moxibustion, in order to provide insights for the establishment of an ideal and feasible mimicking moxibustion model in future RCTs of moxibustion.

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Aged ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Databases, Genetic ; Esophageal Squamous Cell Carcinoma ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Internet ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; User-Computer Interface