ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

A 43-year-old male patient presented with recurrent edema in different anatomical sites for over 10 years, with facial edema worsening 1 day prior to admission. He had been repeatedly admitted to dermatology, general surgery, and emergency departments of external hospitals due to " acute abdomen" and " laryngeal edema, " resistant to antihistamines and glucocorticoid therapy. Physical examination revealed non-pitting swelling of the right upper eyelid, bilateral cheeks, and lips asymmetrically. On the night of admission, he developed acute laryngeal edema with dyspnea, which was promptly treated, leading to clinical stabilization. Laboratory screening during the attack revealed decreased serum complement C4 levels, along with reduced functional activity and concentration of C1 esterase inhibitor, confirming a diagnosis of type 1 hereditary angioedema. The patient received lanadelumab for prophylaxis and achieved satisfactory clinical outcomes. He remains under long-term follow-up.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the correlation between continues glucose monitoring(CGM)parameters and nerve conduction velocity(NCV)in patients with diabetic peripheral neuropathy(DPN).Methods A total of 180 T2DM patients who visited our Endocrinology Department were enrolled in this study from June 2020 to June 2022 and divided into simple type 2 diabetes mellitus(T2DM)group(n=30)and a T2DM combined with DPN group(DPN,n=150)based on whether they had DPN.The DPN group was further divided into mild DPN subgroup(VPT 16～24 V,n=51),moderate DPN subgroup(VPT 25～39 V,n=67),and severe DPN subgroup(VPT≥40 V,n=32)according to the VPT.Results Compared with T2DM group,DM duration,SUA,TBIL,AST,TC,TG,LDL-C and GSP were increased in DPN group(P<0.05 or P<0.01).MAGE,LAGE,MBG,SDBG and FBG-CV in mild,moderate and severe subgroups of DPN increased in turn(P<0.01),while TIR,MNCV and SNCV decreased in turn(P<0.01).Hierarchical regression model analysis showed that MAGE,LAGE,MBG,FBG-CV were the influencing factors for MNCV and SNCV.Logistic regression analysis showed that MAGE,LAGE,MBG,FBG-CV,MNCV and SNCV were all influencing factors for DPN severity.Interaction analysis showed that MNCV,SNCV,MAGE,LAGE,MBG and FBG-CV all had additive and multiplying interactions on the severity of DPN.Conclusions MAGE,LAGE,MBG,FBG-CV,MNCV,and SNCV are factors that affect the severity of DPN,with additive and multiplicative interactions present.

Objective To evaluate the acute exacerbation of chronic obstructive pulmonary disease(COPD)(AECOPD)status via combining clinical data,lung function parameters with CT radiomic features based on machine learning method.Methods A total of 343 COPD patients,including 158 AECOPD patients and 185 non-AECOPD patients were retrospectively selected and randomly divided into training and testing sets at a ratio of 7∶3.The radiomics features were calculated after automatically delineating the whole lung volume of interest(VOI).Five machine learning methods were used to construct the AECOPD diagnostic model,then the corresponding Radiomics score(Rad-score)was calculated in the training set and was validated in the testing set.The logistic-combined model was established after integrating age,Global Initiative for Chronic Obstructive Lung Disease(GOLD)classification,vital capacity(VC),forced vital capacity(FVC),forced expiratory volume in one second(FEV1),FEV1％pred,FEV1/FVC％,peak expiratory flow(PEF),maximum ventilatory volume(MVV),and Rad-score value.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was calculated to evaluate the evaluated performance of all models.Results The logistic regression model had the best diagnostic performance,with AUC of 0.724 and 0.758 in the training and testing sets,respectively.The performance of the logistic-combined model to diagnose AECOPD was superior to that of the single logistic regression model,with the AUC of 0.777 and 0.760 in the training and testing sets,respectively.Conclusion A combination strategy including clinical data,lung function parameters,and CT radiomics may be helpful to diagnose AECOPD status,with moderate diagnostic performance.

Objective:To analyze changes in energy metabolism and oxylipin metabolism in macrophages after stimulation by Mycobacterium marinum ( M. marinum) using targeted metabolomics, and to provide insights into the mechanisms underlying the immune defense by macrophages against M. marinum infections. Methods:Mouse bone marrow-derived macrophages were obtained from the bilateral femurs of mice, and cultured cells were divided into two groups: the active M. marinum group and the inactivated M. marinum group. Bacterial suspensions were prepared using M. marinum clinical isolates; the active M. marinum group was treated with live M. marinum suspensions for 12 hours, while the inactivated M. marinum group with inactivated M. marinum suspensions for 12 hours. Cell morphology was observed through microscopy, and cell length was measured. Cell lysates collected from both groups were subjected to liquid chromatography-tandem mass spectrometry analysis to detect energy and oxylipin metabolites. A t-test was utilized to compare the lengths of macrophages between the two groups, while principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify differential metabolites. Results:Under the microscope, macrophages in the active M. marinum group formed more granuloma-like cell aggregates compared with those in the inactivated M. marinum group; the macrophages were significantly thinner and longer in the inactivated M. marinum group (439.52 ± 91.67 μm) than in the active M. marinum group (289.96 ± 70.11 μm, P < 0.001). Principal component analysis and orthogonal partial least squares-discriminant analysis of energy metabolism and oxylipin metabolism in macrophages demonstrated good separation between the two groups. As for the energy metabolism, a total of 12 differential metabolites were identified, with the amino acid metabolism showing the most significant changes. Specifically, there was a significant increase in the content of L-citrulline, while the content of L-leucine and serine decreased. As for the oxylipin metabolism, 20 differential metabolites were identified, with the arachidonic acid metabolism showing the most significant changes. Conclusions:Macrophages stimulated by live M. marinum exhibited altered amino acid metabolism and arachidonic acid metabolism compared with those stimulated by inactivated M. marinum, characterized by an increase in L-citrulline content, a decrease in L-leucine and serine levels, and alterations in arachidonic acid content.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Objective:Based on the artificial intelligence (AI) technology in endoscopy and the internet platform, to explore and construct a safe, standardized, scientific and rigorous database for digestive endoscopy, and to provide reference and evidence for the data quality control of AI in digestive endoscopy in China.Methods:After referring to relevant guidelines and standards, data collection and labelling standards of digestive endoscopy of 12 common gastrointestinal diseases were determined. The software of online collection and labelling of multi-center digestive endoscopy data in Shandong Province was developed. Endoscopic equipment with a domestic market share of >5% was used and dozens of experienced endoscopists from 9 medical centers in Shandong Province were uniformly trained for data labelling. From July 2019 to July 2020, the endoscopic examination data from 9 medical centers including Qilu Hospital of Shandong University, Shandong Provincial Hospital , Liaocheng People′s Hospital, Linyi People′s Hospital, Weihai Municipal Hospital, Taian City Central Hospital, Binzhou Medical University Hospital, Yantai Yuhuangding Hospital and Qilu Hospital of Shandong University (Qingdao) were prospectively and continuously collected and labeled. The optimized, desensitized, and generalized data were uploaded to the server. After the file synchronization, data processing, and expert review, a multi-center digestive endoscopy AI database with standard data collection and labelling in Shandong Province was constructed, namely cloud platform. Descriptive methods were used for statistical analysis.Results:The collection and labelling standards for multi-center digestive endoscopy AI data in Shandong province was established. The software of online collection and labelling of multi-center digestive endoscopy AI data in Shandong province was developed. The database in Shandong province was successfully constructed. In the database, 43 010 lesions, 40 353 images, and 11 289 examinations were labeled. Among them, there were 2 906 cases of early esophageal cancer, 2 912 cases of early gastric cancer, 2 397 cases of early colorectal cancer, and 9 773 cases of colorectal polyps (5 539 cases of adenomatous polyps, 1 161 cases of non-adenomatous polyps and 3 073 case of undetermined polyps).Conclusions:The multi-center AI cloud platform for digestive endoscopy in Shandong Province adopts unified standards and collection and labeling software, which ensures the safety and standardization of endoscopy data. It provides a reference and basis for the construction of a quality control system for standardized data collection and labelling of digestive endoscopy AI data in our country and for the third-party data supervision.