[Short-term efficacy and safety of cardiac contractility modulation in patients with heart failure].

Objective: To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure. Methods: This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded. Results: CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions: CCM has better short-term safety and efficacy in patients with heart failure.

[Analysis of factors related to systemic embolism in patients≥75 years old with non-valvular atrial fibrillation].

Objective: To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF). Methods: A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE (n=1 127) and SE (n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results: In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio (OR)=2.75, 95% confidence interval (CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L (OR=2.07, 95%CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L (OR=1.91, 95%CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% (OR=2.45, 95%CI 1.63-3.69, P<0.01), left atrial diameter>40 mm (OR=1.54, 95%CI 1.16-2.07, P=0.003), and CHA2DS2-VASc score≥3 (OR=15.14, 95%CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE (OR=0.28, 95%CI 0.15-0.51, P<0.01). Conclusions: History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA2DS2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

[Expert consensus on late stage of critical care management].

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

[Establishment of a rapid method for detection of influenza A/B virus' antigens].

This study aims to develop a rapid and convenient test card for simultaneous detection of influenza A and influenza B viruses using quantum dot-based immunochromatographic assay. The test card consists of a test strip and a plastic casing. The test strip is composed of absorbent paper, a buffer pad, nitrocellulose membrane (NC membrane), sample pad, quantum dot-labeled antibody pad, and polyvinyl chloride (PVC) board. The NC membrane is coated with mouse monoclonal antibodies against influenza A and influenza B viruses for the T lines (test lines), and reference proteins A and B for the C line (control line). The quantum dot-labeled antibody pad contains mouse monoclonal antibody-quantum dot conjugates against influenza A and influenza B viruses. The results showed that the detection limit of the test card for both viruses ranged from 1.51 ×102 to 2.71×103 TCID50/ml, indicating its sensitivity for accurate detection of influenza A and influenza B viruses without being affected by various variants. The test card exhibited specific reactions with different subtypes of influenza A and influenza B virus culture fluids and showed no cross-reactivity with adenovirus, novel coronavirus, Mycoplasma pneumoniae, respiratory syncytial virus, Staphylococcus aureus, and other pathogens. Overall, the sensitivity and specificity of the test card for simultaneous detection of influenza A and influenza B viruses meet the requirements for clinical use. It offers the advantages of simplicity, rapidity, and no requirement for special equipment, enabling quick auxiliary diagnosis to prevent disease transmission.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

A case of Streptococcus canis bacteremia, osteomyelitis, sacroiliitis, myositis, and abscess.

BACKGROUND: Streptococcus canis is a group G beta-hemolytic Streptococcus species which normally resides on the skin and mucosal surfaces of dogs. Although it rarely causes infection in humans, our case and review of relevant literature demonstrate that this multi-host pathogen may be responsible for metastatic infection. We present an appropriate management strategy in such cases. CASE PRESENTATION: A previously healthy 26-year-old male presented to the emergency department with a 2-day history of erythema, pain, and swelling of the left ankle and foot, consistent with acute cellulitis. The patient was initially discharged home with a plan to complete a course of IV cefazolin as an outpatient, but later recalled after two sets of blood cultures grew gram positive cocci. Blood cultures speciated as Streptococcus canis. This was performed by identifying beta hemolytic strep on blood agar, then typed as Lancefield group G, followed by MALDI-TOF which distinguished S. canis. History was unremarkable except for a 2-week history of lower back pain precipitated by a wrestling injury. There was no canine bite or scratch wound, although the patient lives with a dog. CT spine was obtained which demonstrated right piriformis myositis and S1 osteomyelitis. MRI additionally demonstrated right erector spinae myositis, right sacroiliitis, and multiple collections in the right posterior paraspinal soft tissues. Transthoracic echocardiogram did not demonstrate valvular vegetations. The S. canis isolate was pan-susceptible and the patient was ultimately discharged home and completed a 8-week course of IV penicillin G. After completion of therapy, his symptoms, repeat imaging, and biochemical markers suggested resolution of infection on follow-up. CONCLUSIONS: We suggest that management of S. canis bacteremia should involve consideration of screening for metastatic infection and infectious diseases consultation. However, despite its potential for systemic involvement, S. canis is often susceptible to narrow spectrum antibiotics, and may be treated with penicillins.

[Correlation between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation].

Objective: To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function. Methods: Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events. Results: There were significant differences in gender, type of atrial fibrillation, CHA2DS2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (ß=1.168 P=0.002), and left atrial diameter (OR=1.084, 95%CI 1.019-1.153, P=0.011) and persistent atrial fibrillation (OR=2.323, 95%CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions: Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

The feasibility of dual-energy CT to predict the probability of symptomatic intracerebral haemorrhage after successful mechanical thrombectomy.

AIM: To study the ability of dual-energy computed tomography (DECT) after successful mechanical thrombectomy (MT) to predict symptomatic intracerebral haemorrhage (sICH) in anterior circulation acute ischaemic stroke (AIS). MATERIALS AND METHODS: From June 2018 to February 2020, 102 AIS patients with DECT performed immediately after successful MT were enrolled prospectively. According to the presence of iodine contrast media extravasation (ICME) on DECT and subsequent sICH development, patients were classified into four groups. The neurological outcome was compared among groups. Imaging parameters, together with clinical factors, were investigated for sICH prediction based on a linear logistic regression model after class-imbalance resolved by Synthetic Minority Sampling Technique (SMOTE) method. RESULTS: Among 102 patients, patients (14.7%, 15/102) with the presence of sICH experienced worse outcomes than others without sICH (p<0.001). No case without ICME was observed with sICH development (0/102). The parameters derived from DECT have excellent performance for sICH prediction after successful MT, which is better than clinical predictive model boosted data (area under the curve [AUC]: DECT 0.87 versus clinical prediction 0.65), cross-validation results (AUC: DECT 0.87 versus clinical prediction 0.65), and original data (AUC: DECT 0.85 versus clinical prediction 0.68). By combining clinical and radiological parameters, the predictive performance for sICH could be further improved with an AUC of 0.90 (95% CI: 0.85-0.96). CONCLUSIONS: Based on DECT parameters acquired immediately after successful MT, the present model was more efficient than the clinical model for accurate prediction of sICH. Rho and ICME volume appeared to be the best parameters for predicting sICH using DECT.

[Several key points that need to be concerned in the clinical application of ceftazidime/avibactam].

Ceftazidime/avibactam is a new enzyme inhibitor combination medication composed of ceftazidime and avibactam. It forms an enzyme-inhibitor complex by covalently binding ß-lactamase, which can effectively restore the antibacterial activity of ceftazidime against a variety of carbapenemase-producing enterobacteriaceae strains, covering Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Klebsiella pneumonia (CRKP) and other common drug-resistant gram-negative bacteria infections. The related issues of anti-infective effects of ceftazidime/avibactam on lung infections, abdominal infections, bloodstream infections, urinary tract infections and other different infections were discussed in this article. The clinical safety and indications of ceftazidine/avibatan were referred in the article.

Adipokinetic hormone enhances CarE-mediated chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens.

Adipokinetic hormone (AKH), the principal stress-responsive neurohormone in insects, has been implicated in insect responses to insecticides. However, the functionality of AKH and its mode of signalling in insecticide resistance are unknown. Herein, we demonstrated that the enhanced activity of carboxylesterases (CarEs) is involved in the chlorpyrifos resistance in Nilaparvata lugens [brown planthopper (BPH)]. Chlorpyrifos exposure significantly induced the expression of AKH and its receptor AKHR in the susceptible BPH (Sus), and these two AKH signalling genes were over-expressed in the chlorpyrifos-resistant strain (Res) compared to Sus. RNA interference (RNAi) against AKH or AKHR decreased the CarE activity and suppressed the BPH's resistance to chlorpyrifos in Res. Conversely, AKH peptide injection elevated the CarE activity and enhanced the BPH's survival against chlorpyrifos in Sus. Furthermore, five CarE genes were identified to be positively affected by the AKH pathway using RNAi and AKH injection. Among these CarE genes, CarE and Esterase E4-1 were found to be over-expressed in Res compared to Sus, and knockdown of either gene decreased the BPH's resistance to chlorpyrifos. In conclusion, AKH plays a role in enhancing chlorpyrifos resistance in the BPH through positive influence on the expression of CarE genes and CarE enzyme activity.

Lee Silverman Voice Treatment for dysarthria in patients with Parkinson's disease: a systematic review and meta-analysis.

Approximately 89% of patients with Parkinson's disease (PD) suffer from dysarthria. Lee Silverman Voice Treatment (LSVT), a behavioral therapy, aims to improve speech and voice functions. The objective was to assess the effectiveness of LSVT compared with other/no speech interventions for dysarthria in patients with PD. Electronic databases, including PubMed, Embase and the Cochrane Library, were searched. The publication date of all included studies was before 6 March 2020. Only randomized controlled trials (RCTs) that evaluated the LSVT intervention compared with other/no speech intervention were considered. The data obtained from the included studies were described and the mean differences were calculated. Eight RCTs were included in this meta-analysis comparing LSVT with other/no speech interventions. In the comparison of LSVT versus no intervention, vocal intensity for sustained 'Ah' phonation, reading the 'Rainbow passage', monologue and describing a picture increased by 8.87, 4.34, 3.25 and 3.31 dB, respectively, after 1 month of therapy. Compared with the respiratory therapy group, the LSVT group also showed significant improvement in vocal intensity for sustained 'Ah' phonation, reading the 'Rainbow passage' and monologue immediately after treatment (13.39, 6.66 and 3.19 dB). Positive improvement still existed after 24 months. There was no difference in the therapeutic effect between face-to-face and online LSVT. The effectiveness of LSVT for dysarthria in patients with PD was verified in these trials. However, future RCTs with sufficient participants are essential to evaluate the effectiveness of LSVT for dysarthria.

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer.

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway analysis were employed to explore the potential regulatory relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues was higher than that of normal tissues (p<0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (p<0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW 1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (p<0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW 1990 cells and PANC-1 cells (p<0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (p<0.05). The colony formation was notably inhibited in the shCDCA3 group relative to the shCtrl group in SW 1990 cells (p<0.05). Moreover, the tumor growth was evidently suppressed in the shCDCA3 group compared with the shCtrl group in vivo (p<0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

[The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

[A novel mutation of SCN4A gene causes hypokalemic periodic paralysis in a Chinese family].

Objective: To report a Chinese family with hypokalemic periodic paralysis (HOKPP) and investigate the clinical and pathogenic gene characteristics of the family. Methods: The clinical, electrophysiological and pathological data of the proband of the family were analyzed, and the information of the family was investigated in detail. The peripheral venous blood of the six members of the family was collected and their genomic DNA was extracted. The genes related to periodic paralysis analysis of the proband were performed by the second generation sequencing. The pathogenicity of the mutant protein was respectively analyzed by the bioinformatics software SIFT, Polyphen2 and Mutation Tasker. The cosegregation analysis of phenotype and genotype of the family was performed by the first generation sequencing. Results: There were 3 patients in the family with the onset age of 21 to 42 years old. All the patients manifested with vomiting as the first symptoms, then presented with muscle weakness accompanied by muscle soreness. The muscle weakness gradually relieved in 3 to 5 days. Creatine kinase (CK) of the proband significantly increased. Electromyographic exercise test was positive, however, electromyography and muscle pathological analysis were normal. The genes related to periodic paralysis analysis of the proband found a novel mutation (c.2458A>T (p.N.820Y)) of SCN4A gene which was located in the conservative region. The function analysis showed it was a pathogenic mutation. Moreover, the first generation sequencing confirmed that the mutation was cosegregated with patients in the family. Meanwhile, it was found that the proband's son carried the same mutation, but without any symptom, indicating that he was a pre-symptomatic patient. Conclusions: Vomiting can be one of the symptoms of the patients with HOKPP. The novel mutation of SCN4A gene c.2458 A>T is the pathogenic mutation of the family. Patients with periodic paralysis should be tested for blood potassium and genes as early as possible to facilitate early diagnosis and genetic counseling.

[Efficacy and safety of ruxolitinib in the salvage treatment of chronic graft versus-host disease].

Objective: To investigate the efficacy and safety of low-dose Ruxolitinib in the treatment of patients with chronic graft-versus-host disease (cGVHD) and refractory to the first-line and/or second-line drugs after allogeneic hematopoietic stem cell transplantation. Methods: The clinical data was retrospectively analyzed of patients diagnosed with cGVHD in Anhui Provincial Hospital from July 9, 2018 to May 23, 2019. They were refractory to first-line and second-line drugs and were given a low-dose of Ruxolitinib (a dose of 5 mg twice daily if body weight ≥ 25 kg and 2.5 mg twice daily if body weight<25 kg). There was 2.5 mg reduction per week or every two weeks if the condition improved until withdrawal. The efficacy and safety of Ruxolitinib were retrospectively analyzed weekly or biweekly. If the condition improved, the dosage would be reduced by 2.5 mg weekly or biweekly until discontinuance. Results: A total of 47 patients were included in the study,and the median time of taking Ruxolitinib was 55 (21-154) days. The median time of taking effect was 14(7-28) days. The overall response rate was 87.2% (41/47). The complete response rate was 63.8% (30/47) and the partial response rate was 23.4%(11/47). Among them, 13 cases were mild and the overall response rate was 100%(13/13). Twenty one cases were moderate and the overall response rate was 90.5%(19/21). Thirteen cases were severe and the overall response rate was 69.2%(9/13). The highest overall response rate of all organs the was 100% in the gastrointestinal tract (7/7), and it was 95.8%(23/24) for the skin, 83.3%(5/6) for the liver and 76.9%(10/13) for the lung. The highest rate of complete organ response was 95.8% for skin. Eight patients (17%) developed cytopenia, of which 2(4.2%) were with a decrease of 3-4 degree hemoglobin. Recrudescence of cytomegalovirus occurred in 3 patients (6.4%). After withdrawal of Ruxolitinib, 6 patients (12.7%) had recurrence of cGVHD. The median time to relapse was 35.5(7-90) days. All of their conditions were improved after addition of Ruxolitinib. The median time of response was 7(5-14) days. The median follow-up was 208(33-412) days. Three patients(6.4%) died, and all of them died of severe pulmonary infection. Three patients (6.4%) had relapse of primary disease. The 6-month overall survival rate was 95.7%. Conclusion: Low-dose Ruxolitinib has good efficacy and safety in the treatment of cGVHD.

[Progress in research on the relationship between Helicobacter pylori infection and cardiovascular diseases and its risk factors].

In recent years, the high infection rate of Helicobacter pylori and its impact on cardiovascular disease have attracted public attention. It may directly affect coronary heart disease, stroke, etc. through various mechanisms such as inflammation, immune response, and damage to endothelial cells. It could also play an important role in the formation of cardiovascular disease risk factors such as atherosclerosis, hypertension, hyperhomocysteinemia, and dyslipidemia. However, domestic and international research results are still inconsistent, and a large number of experiments are still required to confirm it to take effective measures to control the incidence of cardiovascular disease. This article reviews the prevalence of Helicobacter pylori and cardiovascular disease, the interaction mechanisms and the status of relevant domestic and international researches.

[Analysis of 6344 cases of hospitalized migrant workers with pneumoconiosis].

Objective: To analyze the situation of hospitalized migrant workers with pneumoconiosis in Hunan Province, and to provide reference for the prevention and treatment of pneumoconiosis. Methods: In July 2019, the data of pneumoconiosis migrant workers hospitalized in Hunan Prevention and Treatment Institute for Occupational Diseases from February 2017 to February 2019 were retrospectively analyzed, and the general situation, region distribution, diagnosis and complications were analyzed. Results: From February 2017 to February 2019, a total of 6344 migrant workers with pneumoconiosis were treated, mainly distributed in Zhuzhou city (1283 cases, 20.22%) , Yiyang city (1048 cases, 16.52%) and Loudi city (783 cases, 12.34%) . Coal worker's pneumoconiosis (4242 cases, 66.87%) and silicosis (2089 cases, 32.93%) were the main types of pneumoconiosis. Among them, 1433 cases (22.59%) were in stage I, 1318 cases (20.77%) were in stage II, and 3593 cases (56.64%) were in stage III. The age of the patients was mainly between 41-60 years old (4584 cases, 72.26%) . 3869 patients (60.99%) had complications and chronic obstructive pulmonary disease (3046 cases, 48.01%) and pulmonary infection (1703 cases, 26.84%) were the most common complications. There were 1510 patients (23.80%) who had two or more complications. There were significant differences in the number of complications among patients with different diagnosis stages and age stages (χ(2)=764.43, 90.24, P<0.01) . Conclusion: Coal worker's pneumoconiosis and silicosis are the main types of pneumoconiosis among hospitalized migrant workers in Hunan Province, and most patients were in stage III. Older patients with higher pneumoconiosis stage have more complications, early diagnosis and treatment should be taken.

(CAG)n loci as genetic modifiers of age at onset in patients with spinocerebellar ataxia type 1 from mainland China.

BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1 patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.

The value of detecting pepsinogen and gastrin-17 levels in serum for pre-cancerous lesion screening in gastric cancer.

The aim of the study was to estimate the value of detecting pepsinogen (PG) I, PGII, and gastrin-17 (G-17) levels in serum for chronic atrophic gastritis (CAG) screening and to determine the clinical applicability of combined measurement of serum G-17, pepsinogens (PGI, PGII) and PGI/PGII ratio (PGR) as a screening test for CAG. The PGI, PGII, and G-17 levels were detected by ELISA in 68 patients with CAG and 86 healthy volunteers who underwent gastroscopy for gastroduodenal diseases at Taizhou Municipal Hospital between January 2016 and December 2016. Concentrations of all measured serum markers were lower in patients with CAG in comparison to healthy volunteers and achieved statistical significance (P<0.01) in PGI (93.25 vs 126.98) and PGR (12.67 vs 17.09). Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off values for PGI, PGII, PGR, and G-17 at 98.10 µg/l, 6.92 ng/l, 15.77 and 1.94 pmol/l, with sensitivities of 72.10%, 58.10%, 61.60%, and 59.30% and specificities of 61.8%, 51.50%, 77.90%, and 55.90%, respectively. The areas under the curve (AUCs) of PGI, PGR, and G-17 were 0.728, 0.726, and 0.556, respectively. The increase of AUC was observed only in PGR and G-17 combination (0.741) with increased sensitivity (69.10% vs 61.60%) of screening for CAG, whereas the specificity was reduced (72.10% vs 77.90%) in comparison to PGR alone. Combination of serum indicators can raise the diagnosis accuracy of CAG in some respects. However, further research including a larger sample size is necessary in order to accurately determine the sensitivity and specificity of combined detection of serum indicators.

Alteration of the phagocytosis and antimicrobial defense of Octodonta nipae (Coleoptera: Chrysomelidae) pupae to Escherichia coli following parasitism by Tetrastichus brontispae (Hymenoptera: Eulophidae).

Although parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.