A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

Magnetic resonance Index of Activity (MaRIA) is reliable in assessing response to treatment in patients with Crohn's disease (CD).

AIM: To assess the accuracy of Magnetic Resonance Index of Activity (MaRIA) in evaluating therapeutic efficacy in Crohn's disease (CD) patients with different activity levels using ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Forty-eight patients underwent magnetic resonance enterography (MRE) and ileocolonoscopy at baseline, week 26, and week 52, along with the Simple Endoscopic Score for Crohn's Disease (SES-CD) and MaRIA scores. According to the SES-CD score at baseline, all patients were subdivided into mild, moderate, and severe activity subgroups. The identification of endoscopic mucosal healing (MH) was explored primarily. Moreover, the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) levels were collected and analysed. RESULTS: MaRIA correlated significantly with SES-CD and CRP at baseline, week 26, and week 52. The discrepancies in MaRIA and SES-CD were statistically significant before and after treatment. MaRIA = 24.43 and ΔMaRIA = 12.77 as the cut-off points were found to have high diagnostic accuracy for predicting MH. MaRIA (p<0.001), SES-CD (p<0.001), CRP (p<0.05), ESR (p<0.05), and CDAI score (p<0.05) in patients with MH were considerably decreased compared to those in patients without MH. CONCLUSIONS: MRE has good application value in evaluating the therapeutic response of CD patients treated with biological agents. MaRIA is a reliable indicator in the follow-up of CD patients, which is strongly correlated with SES-CD, and it has high accuracy in predicting endoscopic MH.

[Exploration and practice of cardio-oncology].

With the improvement of oncology diagnosis and treatment, the survival time of cancer patients has been significantly prolonged, and the cancer therapy-related cardiovascular toxicity such as radiotherapy, chemotherapy, immunotherapy, and surgery are becoming more and more prominent, and it is in this context that the germ of Cardio-Oncology exploration has come into being. The multidisciplinary Cardio-Oncology team aims to establish a multidisciplinary prevention and control system to assess patients' baseline risk factors, individualized monitoring, and weighing the risk-benefit ratio of cancer therapy. At present, the connotation of the discipline of Cardio-Oncology has been expanded horizontally and deepened vertically in China, and Cardio-Oncology treatment centers have blossomed all over the country. Moreover, international and domestic scholars continue to improve Cardio-Oncology guidelines and consensus through their own practice, and develop artificial intelligence software to help the development of the discipline. It is believed that in the future, with the training of Cardio-Oncologists and the output of high-quality clinical research evidence, cardiovascular safety of cancer patients can be ensured more scientifically and effectively.

[Serum hepatitis B virus pregenomic RNA profiles in patients with chronic hepatitis B on long-term antiviral therapy].

Objective: To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy. Methods: 100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ (2) test and Fisher's exact test were used to compare categorical variables. Results: HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks (n = 54) during subsequent treatment compared to those who did not (n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients (P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy (r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion: HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

[An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor].

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group (n=39) and non-tumor residual group (n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor (OR=16.852, 95%CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Nonreciprocal Phonon Propagation in a Metallic Chiral Magnet.

The phonon magnetochiral effect (MChE) is the nonreciprocal acoustic and thermal transports of phonons caused by the simultaneous breaking of the mirror and time-reversal symmetries. So far, the phonon MChE has been observed only in a ferrimagnetic insulator Cu_{2}OSeO_{3}, where the nonreciprocal response disappears above the Curie temperature of 58 K. Here, we study the nonreciprocal acoustic properties of a room-temperature ferromagnet Co_{9}Zn_{9}Mn_{2} for unveiling the phonon MChE close to room temperature. Surprisingly, the nonreciprocity in this metallic compound is enhanced at higher temperatures and observed up to 250 K. This clear contrast between insulating Cu_{2}OSeO_{3} and metallic Co_{9}Zn_{9}Mn_{2} suggests that metallic magnets have a mechanism to enhance the nonreciprocity at higher temperatures. From the ultrasound and microwave-spectroscopy experiments, we conclude that the magnitude of the phonon MChE of Co_{9}Zn_{9}Mn_{2} mostly depends on the Gilbert damping, which increases at low temperatures and hinders the magnon-phonon hybridization. Our results suggest that the phonon nonreciprocity could be further enhanced by engineering the magnon band of materials.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

Dung treated by high-temperature composting is an optimal bedding material for suckling calves according to analyses of microbial composition, growth performance, health status, and behavior.

Bedding materials are important for suckling buffalo calves. Treated dung has been used as a bedding material for dairy cows but the lack of an appropriate safety assessment limits its application. In this study, we evaluated the feasibility of treated dung (TD) as a bedding material for suckling calves by comparing TD with rice husk (RH) and rice straw (RS) bedding materials. The TD was prepared through high-temperature composting by Bacillus subtilis. Thirty-three newborn suckling buffalo calves (Bubalus bubalis, 40.06 ± 5.79 kg) were randomly divided into 3 bedding material groups (TD, RH, and RS) and bedded with 1 of the 3 bedding materials for 60 d. We compared cost, moisture content, bacterial counts, and microbial composition of the 3 bedding materials, and investigated growth performance, health status, behavior, rumen fermentation, and blood parameters of bedded calves. The results showed that TD contained the fewest gram-negative bacteria and coliforms on d 1 and 30 and the lowest relative abundance of Staphylococcus throughout the experiment. The RH and TD bedding materials had the lowest cost. Calves in the TD and RS groups showed a higher dry matter intake, and final body weight and average daily gain in the TD and RS groups tended to be higher than in the RH group. Calves in the TD and RS groups had a lower disease incidence (diarrhea and fever), fewer antibiotic treatments, and lower fecal score than calves in the RH group. Higher contents of IgG, IgA, and IgM were observed in calves of the TD and RS groups than in calves of the RH group on d 10, indicating higher immune ability in TD and RS groups. Furthermore, TD bedding increased the butyric acid content in the calf's rumen, whereas RS bedding increased the acetate content, which might be attributed to the longer time and higher frequency of eating bedding material in the RS group. Considering all of the above indicators, we concluded that TD is the optimal bedding material for calves based on economics, bacterial count, microbial diversity, growth performance, and health status. Our findings provide a valuable reference for bedding material choice and calf farming.

[Clinical analysis of immunotherapy rechallenge in advanced gastric cancer].

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

[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.

[Comparison of the therapeutic effects of optic nerve sheath fenestration and medication on papilledema due to cerebral venous thrombosis].

Objective: To compare the therapeutic effects of optic nerve sheath fenestration (ONSF) and medication on papilledema induced by cerebral venous thrombosis (CVT). Methods: Patients with papilledema induced by CVT in Beijing Tiantan Hospital and Xuanwu Hospital from January 2017 to July 2022 were retrospectively enrolled and were divided into two groups according to the treatment strategies they underwent, with 76 cases (107 eyes) in ONSF group and 35 cases (69 eyes) in medication group. The degree of papilledema was evaluated by the modified Frisén's grading (grade 0-1 was defined as mild, grade 2-3 was moderate, and grade 4-5 was severe edema). The mean defect (MD) of visual field, the degree of papilledema, and the mean retinal nerve fiber layer (RNFL) thickness in different subgroups were compared between baseline versus 1 month after ONSF or medication. Results: There were 76 cases in ONSF group (26 males and 50 females), and aged (35.3±11.4) years. Meanwhile, there were 35 cases in medication group (22 males and 13 females), and aged (35.2±11.0) years. Compared with baseline, MD were improved in both moderate [(-8.4±6.6) vs (-11.8±8.6) db, P=0.021] and severe [(-8.1±5.3) vs (-11.4±6.9) db, P<0.001] papilledema subgroups after ONSF, while there was an improvement in mild papilledema subgroup [(-1.5±5.3) vs (-3.4±5.1) db, P<0.001] after medication. The papilledema (Frisén's scores) in both ONSF group (P<0.001) and medication group (P=0.010) was improved. Compared with baseline, the mean RNFL decreased in mild [(78.5±13.5) vs (91.0±17.4) µm, P=0.002], moderate [(126.6±67.6) vs (154.8±77.9) µm, P=0.011] and severe [(179.0±70.9) vs (230.6±89.7) µm, P=0.001] papilledema subgroups after ONSF, while the mean RNFL decreased [(142.0±29.3) vs (158.8±22.7) µm, P=0.020] in moderate papilledema subgroup after medication. Conclusions: ONSF might attenuate CVT-mediated papilledema, and improve the visual function in patients with moderate and severe papilledema. Likewise, patients with mild papilledema could also get benefit from medication.

[Clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae].

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ2=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.

[Current status of vaccination services for adults in urban and rural areas of nine provinces in China from 2019 to 2021].

Objective: To understand the current situation of vaccination services for adults in China, explore how to establish a stable and efficient vaccination service system for adults, and provide reference for formulating corresponding policies. Methods: The vaccination information systems of nine provinces in China were used to obtain information on urban and rural vaccination of influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPV23), and human papillomavirus vaccine (HPV) from 2019 to 2021. The indicator, vaccination rate/full vaccination rate, was used for statistical description. Results: The vaccination rate/full vaccination rate of the three vaccines in eastern China was generally higher than that in central and western China. The vaccination rate/full vaccination rate in urban areas was generally higher than that in rural areas. From 2019 to 2021, the vaccination rates of influenza vaccine among people aged 60 years and above in urban and rural areas were 2.96%, 6.29%, 6.14% and 1.29%, 2.58%, 2.94%, respectively. The vaccination rates of the PPV23 among people aged 60 years and above in urban and rural areas increased year by year, with rates of 0.38%, 1.05%, 1.15% and 0.14%, 0.49%, 0.59%, respectively. From 2019 to 2021, the HPV coverage of female adults aged 27-45 years in urban and rural areas increased year by year, with rates of 0.46%, 0.93%, 1.88% and 0.17%, 0.40%, 1.08%, respectively. Conclusion: The vaccination rates of influenza vaccine,PPV23 vaccine and HPV vaccine for adults in China are relatively low, with higher rates in the eastern region than in the central and western regions, and higher rates in urban areas than in rural areas. It is recommended to formulate corresponding health and economic policies and explore a suitable vaccination service system for adults in China to improve vaccination rates.

[A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma].

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

[Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma].

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model].

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

Nomogram to predict haemorrhagic transformation after stroke thrombolysis: a combined brain imaging and clinical study.

AIM: To construct a novel nomogram by integrating computed tomography perfusion (CTP) and clinical parameters for individualised prediction of haemorrhagic transformation (HT) in intravenous thrombolysis (IVT)-treated acute ischaemic stroke (AIS) patients. METHODS: Anterior circulation AIS patients who underwent IVT at a single centre from January 2018 to June 2020 were reviewed retrospectively. The CTP parameters of two regions of interest (ROI), the entire perfusion lesion areas, and the infract core areas, were assessed. HT was documented by follow-up CT 24 ± 2 h after IVT. Multivariable logistic regression was conducted by including clinical variables and CTP parameters to identify the independent predictors of HT. A nomogram was developed based on the independent predictors. The discriminative value and calibration of the nomogram were tested by concordance indexes (C-indexes) and calibration plots. Internal validation was performed using fivefold cross-validation. RESULTS: The nomogram was generated using the complete data from 341 patients. Seven variables were included in the final nomogram, including: the relative cerebral blood volume (rCBV), permeability surface (PS), and relative PS (rPS) in infract core areas, the relative time to maximum (rTmax) and rPS in entire perfusion lesion areas, the National Institutes of Health Stroke Scale (NIHSS), and atrial fibrillation (AF). The C-indexes were 0.815 and 0.817 for the nomogram and internal validation. The calibration plots showed excellent agreement. CONCLUSION: This is the first study establishing a nomogram based on CTP and clinical parameters to predict HT after stroke thrombolysis.

[Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom].

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.