Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis.

OBJECTIVE: There is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG). METHODS: A total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination. RESULTS: Of 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization. CONCLUSION: Our results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

[The application value of shear wave dispersion and shear wave elastography combined with serological indicators in the evaluation of liver fibrosis].

Objective: To explore the application value of shear wave dispersion (SWD) and shear wave elastography (SWE) combined with serological indicators in the evaluation of liver fibrosis. Methods: A total of 219 patients with liver disorders who underwent liver biopsy were prospectively collected in Huashan Hospital, Fudan University from January 2021 to September 2022, including 130 males and 89 females, aged from 18 to 76 (42±12) years. All patients underwent SWD and SWE examinations before liver biopsy. Serological indicators including alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP)) and γ-glutamyl transpeptadase (GGT) were also collected. Based on pathological diagnosis of liver fibrosis stage (from S0 to S4), the distribution of dispersion slope and liver elastic modulus at different fibrosis stages were analyzed in all patients. All patients were divided 7: 3 into training set (156 cases) and validation set (63 cases) in chronological order. In training set, factors influencing liver fibrosis≥S2 stage and S4 stage were analysed using binary logistic regression. The predictive models were established for diagnosing liver fibrosis≥S2 stage and S4 stage by using R language, and the models were evaluated by the area under curve (AUC) and calibrated for validation. Results: The dispersion slope and elastic modulus increased with the severity of fibrosis, with statistically significant differences in different fibrosis stages (both P<0.001). In training set, dispersion slope, elastic modulus, ALT, AST, and GGT were influential factors in liver fibrosis≥S2 stage and S4 stage(both P<0.05), and prediction models were constructed based on these indicators. In training set, the AUCs of the predictive model, SWD and SWE for diagnosingliver fibrosis≥S2 stage were 0.743 (95%CI: 0.665-0.821), 0.709 (95%CI: 0.628-0.790) and 0.725 (95%CI: 0.647-0.804), respectively; for diagnosing liver fibrosis S4 stage, the AUCs were 0.988 (95%CI: 0.968-1.000), 0.908 (95%CI: 0.852-0.963) and 0.974 (95%CI: 0.945-1.000), respectively. In validation set, the AUC of the predictive model, SWD and SWE for diagnosing liver fibrosis≥S2 stage were 08.735 (95%CI: 0.612-0.859), 0.658 (95%CI:0.522-0.793) and 0.699 (95%CI:0.570-0.828), respectively; for diagnosing liver fibrosis S4 stage, the AUC were 0.976 (95%CI: 0.937-1.000), 0.872 (95%CI: 0.757-0.988) and 0.948 (95%CI: 0.889-1.000), respectively. The calibration curves of the prediction models were consistent in the training and validation sets. Conclusion: The predictive model of SWD and SWE combined with serological indicators is helpful in the diagnosis of stage of liver fibrosis non-invasively.

[Constructing the Bayesian network models to explore the factors related to glomerular and tubular injury].

Objective: To construct Bayesian network (BN) models to explore the factors related to glomerular injury (GI) and tubular injury (TI). Methods: A cross-sectional study was carried out. From April to November 2019, Shanxi Provincial People's Hospital performed an opportunistic screening for chronic kidney disease in 10 counties of Shanxi Province. The general data and laboratory results of blood and urine samples were collected. Chi-square test and logistic regression were used to explore the related factors of GI and TI, which were included in the construction of BN models with max-min hill-climbing (MMHC) algorithm. Results: A total of 12 269 participants were included, there were 5 198 males and 7 071 females, with a median age of 58 (40-91) years. The prevalence of GI and TI was 12.7% (1 561/12 269) and 11.6% (1 425/12 269), respectively. The BN model consisted of 8 nodes and 10 edges for GI, and 11 nodes and 17 edges for TI, respectively. BN models showed that age and glycated hemoglobin were direct related factors for GI, while gender and fasting blood glucose were indirect related factors for GI. Age, gender, fasting blood glucose and glycosylated hemoglobin were direct related factors for TI. Additionally, the area under the receiver operating characteristic curve (AUC) was 0.761 (95%CI: 0.746-0.777) and 0.753 (95%CI: 0.736-0.769) for GI and TI BN models, respectively. Conclusions: BN models allow for identifying the complex network relationships among the factors related to GI and TI. Meanwhile, Bayesian risk reasoning can provide reference value for the clinical prevention of GI and TI.

[Clinical and biological features and prognosis of patients with leukemic non-nodal mantle cell lymphoma].

Objective: To investigate the clinical, biological and prognostic characteristics of leukemic non-nodal mantle cell lymphoma (nnMCL). Methods: The clinical data of 14 patients with nnMCL and 238 patients with classical mantle cell lymphoma (cMCL) in Blood Diseases Hospital, Chinese Academy of Medical Sciences from November 2000 to October 2020 were retrospectively analyzed. Among the 14 patients with nnMCL, there were 9 males and 5 females, with the age [M (Q1, Q3)] of 57.5 (52.3, 67.0) years. Among the 238 patients with cMCL, there were 187 males and 51 females, with the age of 58.0 (51.0, 65.3) years. The clinical and biological characteristics of the two groups were recorded and compared. Follow-up and efficacy evaluation were conducted by re-examination during hospital stay and telephone follow-up and so on. Results: The proportion of CD200 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [14.6% (19/130)] (P=0.001). The proportion of CD23 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [13.5% (23/171)] (P<0.001). The proportion of CD5 expression in nnMCL patients was 10/14, which was lower than that in cMCL patients [97.4% (184/189)] (P=0.001). The proportion of CD38 expression in nnMCL patients was 4/14, which was lower than that in cMCL patients [69.6% (112/161)] (P=0.005). The expression proportion of sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) in nnMCL patients was 1/5, which was lower than that in cMCL patients [77.9% (60/77)] (P=0.014). The proportion of immunoglobulin heavy chain variable region (IGHV) mutations in nnMCL patients was 11/11, which was higher than that in cMCL patients [26.0% (13/50)] (P<0.001). As of April 11, 2021, the follow-up time for nnMCL and cMCL patients was 31 (8-89) months and 48 (0-195) months, respectively. Among the 14 nnMCL patients, 6 patients were still under observation, and 8 patients were treated. The overall response rate (ORR) was 8/8, including 4 patients with complete remission and 4 patients with partial response. The median overall survival and median progression-free survival were not reached in nnMCL patients. In the cMCL group, 50.0% (112/224) patients achieved a complete response, 24.6% (55/224) patients achieved a partial response, and ORR was 74.6% (167/224). There was no statistically significant difference in ORR between the two groups (P=0.205). Conclusions: nnMCL patients have an indolent progression, with higher expression rates of CD23 and CD200 and lower expression rates of SOX11, CD5 and CD38. Most patients have IGHV mutations, with a relatively good prognosis, and"watch and wait"approach is an optional treatment.

[Efficacy and prognosis of infant kidney transplantation].

Objective: To analyze the effect and prognosis of infant kidney transplantation. Methods: Clinical data of 37 cases of infant kidney transplantation under 3 years old in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from June 1, 2017 to July 31, 2022 were retrospectively collected. These 37 cases included 31 primary kidney transplantation and 6 secondary kidney transplantation. Kaplan-Meier method was used to draw the survival curve of the transplanted kidney and the recipient, and the prognosis and complications were analyzed. Median follow-up was 18 months (range: 6-66 months). Results: The recipients were 20 males and 17 females, with a median age of 16 months (range: 2 months, 26 days to 36 months) and a median weight of 8 kg (range: 3.2 to 14.0 kg). The youngest child was only 2 months, 26 days old, and weighed only 3.2 kg. The most common primary disease of recipients was congenital nephrotic syndrome (13 cases, 41.9%). Intra-abdominal transplantation occurred in 19 cases (51.3%) and intra-iliac fossa transplantation occurred in the remaining 18 cases (48.6%). Postoperative renal function recovery was delayed in 7 cases (18.9%), and thrombosis caused renal function loss in 5 cases (13.5%), of which 4 cases received second renal transplantation and were successful. During the follow-up period, there were 11 cases of acute rejection (29.7%) and 6 cases of CMV pneumonia (16.2%). The estimated glomerular filtration rate 1 year after transplantation was higher than that 1 month after surgery [(101.9±22.1) vs (71.1±25.6) ml/(min·1.73m2), P<0.001], and remained constant 2 years after transplantation. Both the 1-year and 2-year survival rates of the transplanted kidney were 85.3%, and both the 1-year and 2-year survival rates of the recipients were 96.8%. Conclusion: Although the implementation of infant kidney transplantation is difficult, it can still achieve relatively satisfactory efficacy and prognosis.

[Occupational protection effect of two protective devices for manual cleaning and oiling of dental handpieces on operators].

Objective: To explore the occupational protective effect of different protective devices on the operators during manual cleaning and oiling of dental handpieces, and to provide a basis for the selection of appropriate protective methods. Methods: From November 2020 to December 2021, 20 high-speed dental handpieces of the same brand were selected and randomly divided into disposable protective bag group and small aerosol safety cabinet group by drawing lots, with 10 in each group. After recording the model, they were distributed to the clinical fixed consulting room for use, and were collected by specially-assigned personnel every day for manual cleaning under the protection of the two devices. By measuring the number of airborne colonies, the concentrations of particulate matter and the satisfaction of operators, the occupational protection effect of the two protective devices on operators was evaluated. Results: Under the protection of the two devices, the average number of airborne colonies after operation was less than 1 CFU/ml. When no protective device was used, the number concentration of particulate matter produced during operation was (21595.70±8164.26) pieces/cm(3). The number concentrations of particles produced by disposable protective bag group [ (6800.24±515.05) pieces/cm(3)] and small aerosol safety cabinet group [ (5797.15±790.50) pieces/cm(3)] were significantly lower than those without any protective device (P<0.001). The number concentration of particle matter of small aerosol safety cabinet group was significantly lower than that of disposable protective bag group (P<0.001). In the satisfaction evaluation of operators, small aerosol safety cabinet group [ (3.53±0.82) points] was significantly better than disposable protective bag group [ (2.23±1.10) points] (P<0.001) . Conclusion: The use of small aerosol safety cabinet during manual cleaning and oiling of dental handpieces has good protective effect, superior safety performance and strong clinical applicability, and has advantages in occupational protection of clinical operators.

[Expression of CD24 gene in human malignant pleural mesothelioma and its relationship with prognosis].

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.

[A case of pulmonary aspergillus infection in underground coal mine workers].

The underground environment is dark and humid, and it is easy to breed pathogenic microorganisms. A lump in the right lung of a coal mine underground transport worker was found druing occupational health examination. CT examination showed that the lump was located in the posterior segment of the upper lobe of the right lung, with point strip calcification, liquefaction necrosis, and proximal bronchial stenosis and occlusion. MRI examination FS-T(2)WI and DWI showed "target sign", annular low signal around the central high signal, and low mixed signal around the periphery, and annular high signal in the isosignal lesions on T(1)WI. Then the pulmonary aspergillus infection was confirmed by pathology.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

[Clinical classification and treatment decision of implant fracture].

OBJECTIVE: To propose a set of two-dimensional clinical classification of fractured implants based on the follow-up of fracturing pattern of implant body and peri-implant bone defect morphology of 32 fractrued implants, and summarize the treatment decisions of fractured implants according to this new set of classification, so as to provide guidance for clinical practice. METHODS: During 25 years of clinical practice, clinical records of 27 patients of 32 fractured implants in 5 481 patients with 10 642 implants were made. The fracturing pattern of implant body, implant design, peri-implant bone defect morphology and treatment options were analyzed. A set of two-dimensional clinical classification based on the morphology and bone absorption of implant fracture was proposed. The treatment decision-making scheme based on the new classification of implant fracture was discussed. RESULTS: In the new classification system, vertical fracture of implant neck (Type 1 of implant fracture morphology, F1) and horizontal fracture of implant neck (Type 2 of implant fracture morphology, F2) were common, accounting for 50% and 40.6% respectively, while deep horizontal fracture of implant body (Type 3 of implant fracture morphology, F3) (9.4%) were rare, while the three types of bone defects (D1, no bone defect or narrow infrabony defects; D2, wide 4-wall bone defects or cup-like defects, D3, wide 3-wall or 2-wall defects) around implants were evenly distributed. In the two-dimensional classification system of implant fracture, F1D1 (31.3%) and F2D2 (25%) were the most frequent. There was a significant positive correlation between F1 and D1 (r=0.592, P < 0.001), a significant positive correlation between F2 and D2 (r=0.352, P=0.048), and a significant negative correlation between F1 and D2 (r=-0.465, P=0.007). The most common treatment for implant fracture was implant removal + guided bone regeneration(GBR) + delayed implant (65.6%), followed by implant removal + simultaneous implant (18.8%). F1D1 type was significantly related to the treatment strategy of implant removal + simultaneous implantation (r=0.367, P=0.039). On this basis, the decision tree of implant fracture treatment was summarized. CONCLUSION: The new two-dimensional classification of implant fracture is suitable for clinical application, and can provide guidance and reference for clinical treatment of implant fracture.

[Application evaluation of prefabricated rigid connecting bar in implants immediate impression preparation of edentulous jaw].

OBJECTIVE: To compare the operation complexity and accuracy of traditional splint impression technique and impression technique with prefabricated rigid connecting bar system for full-arch implants-supported fixed protheses in vitro. METHODS: Standard mandibular edentulous model with six implant analogs was prepared. The implants were placed at the bone level and multiunit abutments screwed into the implants. Two impression techniques were performed: the traditional splint impression technique was used in the control group, and the rigid connecting bar system was used in the test group. In the control group, impression copings were screwed into the multiunit abutments and connected with autopolymerizing acrylic resin. Open tray impression was fabricated with custom tray and polyether. In the test group, cylinders were screwed into the multiunit abutments. Prefabricated rigid bars with suitable length were selected and connected to the cylinders with small amount of autopolymerizing acrylic resin, and open tray impression was obtained. Impression procedures were repeated 6 times in each group. The working time of the two impression methods were recorded and compared. Analogs were screws into the impressions and gypsum casts were poured. The gypsum casts and the standard model were transferred to stereolithography (STL) files with model scanner. Comparative analysis of the STL files of the gypsum casts and the standard model was carried out and the root mean square (RMS) error value of the gypsum casts of the control and test groups compared with the standard model was recorded. The trueness of the two impression techniques was compared. RESULTS: The work time in the test group was significantly lower than that in the control group and the difference was statistically significant [(984.5±63.3) s vs. (1 478.3±156.2) s, P < 0.05]. Compared with the standard model, the RMS error value of the implant abutments in the test group was (16.9±5.5) µm. The RMS value in the control group was (20.2±8.0) µm. The difference between the two groups was not significant (P>0.05). CONCLUSION: The prefabricated rigid connecting bar can save the chair-side work time in implants immediate loading of edentulous jaw and simplify the impression process. The impression accuracy is not significantly different from the traditional impression technology. The impression technique with prefabricated rigid connecting bar system is worthy of clinical application.

[Analysis of clinical characteristics and related genetic variation of juvenile myasthenia gravis].

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients.

[Clinical characteristics and outcomes of myasthenia gravis patients with double positive antibodies against acetylcholine receptor and muscle-specific tyrosine kinase].

Objective: To investigate the clinical manifestations, treatment characteristics and outcomes of myasthenia gravis (MG) dually positive for anti-acetylcholine receptor antibody (AChR-Ab) and anti-muscle-specific tyrosine kinase antibody (MuSK-Ab). Method: MG patients hospitalized in the First Affiliated Hospital of Sun Yat-sen University from August 2017 to November 2020 were retrospectively collected. Thirty-four MuSK-Ab positive MG (MuSK-MG) patients, 11 double-antibodies positive MG (DP-MG) patients, and 80 AChR-Ab positive MG (AChR-MG) patients were included and allocated to three different groups. The clinical data of patients in the three groups were collected, and the differences of demographic characteristics, clinical manifestations and treatment outcomes between DP-MG patients and AChR-MG and MuSK-MG patients were analyzed. Result: The proportion of female and male patients in DP-MG group was 7/11 and 4/11 respectively, and the onset age of DP-MG was (41±27) years.The difference in gender distribution between DP-MG and AChR-MG groups was statistically significant (P<0.05). The proportion of extraocular muscle involvement in the DP-MG and MuSK-MG groups (8/11 and 52.9%) was lower than that in the AChR-MG group (83.8%), and the difference was statistically significant (P<0.05). The incidence of myasthenia crisis in DP-MG and MuSK-MG groups (54.5% and 61.8%) were higher than that in AChR-MG group (20.0%), with astatistically significant difference(P<0.05). The positive rate of neostigmine test in DP-MG and MuSK-MG groups(8/11 and 74.2%) were lower than that of AChR-MG group (96.8%), and the positive rate of low frequency repetitive nerve stimulation (RNS) in DP-MG group (5/10) was lower than that in AChR-MG group (85.1%), with statistically significant differences (all P<0.05). MuSK-Ab titer was positively correlated with the course of disease (r=0.466, P<0.05), and antibody titer decreased after symptom improvement (P<0.05). The response of patients in DP-MG and MuSK-MG groups to cholinesterase inhibitors (2/11 and 9.1%) was worse than that in the AChR-MG group (66.3%), and the incidence of side effects in the two groups (5/11 and 39.4%) was higher than that in the AChR-MG group (15.0%), with statistically significant differences (all P<0.05). There were 4 DP-MG patients underwent thymectomy, and the pathological results detected two cases of thymoma and two cases of thymic hyperplasia. Subsequent follow-up showed that 5 (5/11) DP-MG patients achieved minimal manifestation status or better status. Conclusion: The gender distribution, age of onset, pharmacological characteristics and electrophysiological examination of DP-MG patients were similar to those of MuSK-MG patients, but the severity of DP-MG patients was between that of AChR-MG and MuSK-MG patients.

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

[A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China].

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

[A retrospective controlled study of TACE-HAIC-targeted-immune quadruple therapy for intermediate and advanced-stage hepatocellular carcinoma].

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ2 test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.

[Control study of chest CT imaging features of aluminosis and silicosis patients].

Objective: To understand the chest CT features of aluminosis caused by alumina and to improve the understanding of the imaging findings of alumina pneumoconiosis. Methods: The chest CT findings of 17 cases of alumina-induced pneumoconiosis and 30 cases of silicosis (the control group) diagnosed in Zibo Occupational Disease Prevention Hospital from April 2015 to July 2020 were analyzed retrospectively. The characteristics of fibrosis of the two kinds of pneumoconiosis and the incidence of size, density, distribution, tractive bronchiectasis, pleural thickening and interlobular septal thickening of pneumoconiosis nodules were compared. Results: Alumina pneumoconiosis showed nodules with thickened interlobular septal of 66.67% (12/18) , honeycomb lung of 22.22% (4/18) , ground glass shadow of 61.11% (11/18) , simple nodules of 11.11% (2/18) , and no fusion mass. In the control group, the long-line fibrosis of nodules with thickened interlobular septal were 16.67% (5/30) , 6.67% (2/30) with honeycomb lung and ground glass density shadow, 23.33% (7/30) with fusion mass and 53.33% (16/30) with simple nodule. There were significant differences in CT findings of nodules with thickened interlobular septal, ground glass density shadow, fused mass and simple nodules between the two groups (P<0.05) . The interstitial beaded nodules were seen in 18 cases of alumina pneumoconiosis, 50.00% (9/18) of them were beaded nodules, 61.33% (46/75) of low density nodules and 38.89% (7/18) of central lobular nodules were seen in alumina pneumoconiosis. The average width of nodules was (1.29±0.38) mm. Central lobular nodules were seen in all 30 cases of silicosis, 10.00% (3/30) were mainly beaded nodules, low density nodules were 36.29% (90/248) , and the average width diameter of nodules was (1.85±0.58) mm. There were significant differences between the two groups (P<0.05) . Alumina pneumoconiosis was often accompanied by traction bronchiectasis, pleural thickening and interlobular septal thickening (11, 18, 17 cases, 61.11%, 100.00%, 94.44%) , compared with the control group (9, 18, 18 cases, 30.00%, 60.00%, 60.00%) . The differences were statistically significant (P<0.05) . The maximum CT value of noncalcified mediastinal lymphnodes in alumina pneumoconiosis was (103.43±26.33) HU, which was higher than that of the control group[ (75.22±16.70) HU], and the difference was statistically significant (P<0.05) . Conclusion: Alumina pneumoconiosis chest CT shows slightly low-density beaded nodules, thickened interlobular septal, and pulmonary interstitial fibrosis of ground-glass shadows, mostly combines with stretched bronchiectasis, thickened pleura, and mediastinum increased lymph node density.

Heteroresistant Bacteria Detected by an Extended Raman-Based Antibiotic Susceptibility Test.

Worldwide, multiresistant bacterial strains are emerging at unprecedented rates. This development seriously threatens the ability of humanity to treat even common infections, resulting in disability and death. Furthermore, this development endangers all medical achievements including cancer therapy or organ transplantations. Therefore, the World Health Organization has endorsed antimicrobial resistance as a great threat to humanity. To still allow effective treatment of patients, rapid, automated, and reliable antibiotic susceptibility testing (AST) of bacterial pathogens is essential. Thereby, speed and sensitivity of the AST results are crucial for improving patient care. Here, Raman spectroscopy as a nondestructive technique providing chemical-specific information is employed to monitor the deuterium uptake of metabolically active bacteria during antibiotic treatment, enabling fast and reliable AST. For this purpose, a bulk sample-preparation method was developed, allowing a high-throughput analysis of a significant number of cells. A protocol was developed for Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) reference strains and was tested on 51 clinical isolates with well-characterized resistance phenotypes against ampicillin, ciprofloxacin, meropenem, and vancomycin. Borderline resistant and heteroresistant phenotypes were observed and further investigated. This is of critical importance as the sensitive detection of low-frequency heteroresistance in bacterial populations is a huge challenge. Such isolates seem susceptible but are resistant to treatment in vivo. Automatable analysis detects strong phenotypes within 3 h. On the basis of experimental and modeled data, heteroresistance is estimated to be detectable down to frequencies of 10-6 and investigated on clinical isolates as a proof-of-concept study, but requiring longer incubation time.

RNA interference-mediated knockdown of the transcription factor Krüppel homologue 1 suppresses vitellogenesis in Chilo suppressalis.

Vitellogenesis in holometabolous insects involves the production and secretion of vitellogenin (Vg) and other yolk protein precursors in developing oocyte by the fat body, all of which is predominantly orchestrated by juvenile hormone (JH). Krüppel homologue 1 (Kr-h1) is a zinc finger transcription factor that has been demonstrated to be a JH-early inducible gene and to contribute to reproduction. However, the exact molecular function of Kr-h1 in insect reproduction is poorly understood. In the current study, we used the notorious pest Chilo suppressalis as a model system to investigate the role of Kr-h1 in female reproduction. Cloning and sequencing C. suppressalis Kr-h1 revealed that it shares high identity with its homologues from other lepidopteran insects. Moreover, RNA interference-mediated knockdown of CsKr-h1 substantially reduced the transcription of Vg in the fat body, dramatically decreased yolk protein deposition and also impaired oocyte maturation and ovarian development, indicating that Kr-h1 is indispensable for normal vitellogenesis in C. suppressalis. Based on these results, we conclude that Kr-h1 is crucial to reproduction in insects and that targeting this gene could potentially be a new way to suppress rice pests.