Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95％confidence interval[CI]:0.2—1.0),STE(OR=1.5,95％CI:1.0—2.1),and PIIIP(OR=1.1,95％CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34％and a sensitivity of 96.36％,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.

Objective To establish a noninvasive diagnostic model for liver fibrosis in chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and an age of≤30 years by selecting specific indicators from the commonly used noninvasive indicators such as clinical,biochemical,and imaging indicators,to avoid invasive liver biopsy in such patients to some extent,and to guide the timing of antiviral therapy.Methods A total of 251 CHB patients with normal ALT and an age of≤30 years who underwent liver biopsy in Shenzhen Third People's Hospital and The First Hospital of Changsha from January 2019 to January 2022 were enrolled,with 175 patients in the model group and 76 patients in the validation group,and commonly used clinical indicators were obtained based on clinical experience and related articles.The two-independent-samples t test or the two-independent-samples Mann-Whitney U rank sum test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.A Spearman rank correlation analysis was used to investigate the correlation between each indicator and liver fibrosis and identify the indicators with correlation(P<0.01,r>0.200);a Logistic regression analysis was used to establish a noninvasive diagnostic model,and the receiver operating characteristic(ROC)curve was used to evaluate its performance and perform validation of the model;this model was then compared with the widely used models of aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB-4).The Kappa consistency test was used to investigate the consistency of pathological results.Results A total of 17 commonly used clinical indicators were obtained,among which 9 indicators(ALT,aspartate aminotransferase[AST],gamma-glutamyl transpeptidase[GGT],ferritin[FERR],platelet count[PLT],procollagen type Ⅲ amino-terminal peptide[PⅢP],collagen Ⅳ[CⅣ],HBV DNA,and spleen thickness)were correlated with liver fibrosis(P<0.01,r>0.232).Based on the above indicators,the predictive model was established as P=1/(1+e-γ),γ=-1.902+0.106×AST-0.011×PLT-0.265×HBV DNA+0.059×PⅢP,in which P was the probability for predicting≥S2 liver fibrosis and γ was the predictive index.The comparison between each indicator and the model showed that the model had the largest area under the ROC curve of 0.852,with a sensitivity of 92.7%and a specificity of 76.9%.The model was validated in 76 patients and showed an accuracy of 77.600%.The model was compared with APRI and FIB-4,and the results showed that the model has good accuracy.Conclusion Compared with the models of APRI and FIB-4 commonly used in the world,this model can more accurately judge the degree of liver fibrosis in such patients,thereby replacing liver biopsy to some extent and guiding the timing of antiviral therapy.

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

Objective:To compare the efficacy of articaine infiltration anesthesia and lidocaine nerve block anesthesia in pulpotomy of deciduous mandibular second molars.Methods:Single blind crossover test was used for the pediatric patients who required bilateral de-ciduous mandibular second molar pulpotomy were given articaine infiltration anesthesia and lidocaine nerve block anesthesia respectively before the 2 times of operation.After the injection of anesthetic drugs and dental pulp treatment,the patients'responses to pain were e-valuated through sound,eye and body movements,and Wong-Baker facial pain rating scales.Quantitative comparisons were made.Student's t-test and chi-square test were performed for the collected data.Results:50 pediatric patients who met the inclusion criteria and successfully completed 2 treatments without any missed visits or adverse events.During the process of articaine infiltration anesthe-sia,the scores of the 3 indicators of pain severity,namely sound,eye and body movements,were lower than those of lidocaine nerve block anesthesia(P＜0.05).The analysis of facial pain rating scales also suggested that patients'pain and discomfort during the infiltra-tion anesthesia process with articaine were milder(P＜0.05).During the treatment of pulpotomy,both pain assessment methods showed no statistically significant difference in pain perception between the 2 anesthesia injections(P＞0.05).Conclusion:Articaine infiltra-tion anesthesia may effectively replace lidocaine nerve block anesthesia in pulp treatment of mandibular primary molars.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

Objective:To screen active antibacterial components from licorice extract using BamA and BamD, the core components of Escherichia coli ( E. coli) β-barrel assembly machinery (BAM), as targets in order to combat the increasingly serious problem of antibiotic resistance. Methods:Affinity ultrafiltration combined with high performance liquid chromatography-mass spectrometry (HPLC-MS) was used to screen the potential components interacting with BamA and BamD from licorice extract. Changes in the expression of bamA and bamD genes of E. coli after treatment with the compounds were detected by fluorescence quantitative PCR, and the effects of the compounds on the function of the BAM complex to integrate outer membrane proteins into the bacterial outer membrane were analyzed using an in vitro recombination system. The influence of the compounds on the integrity of bacterial membranes was evaluated through analyzing the accumulation of SDS within the bacterial cells. Results:Bioaffinity ultrafiltration combined with HPLC-MS screening revealed that 18β-glycyrrhetinic acid could interact with BamD. After 18β-glycyrrhetinic acid treatment, the expression of bamA gene increased by 1.5 times, and the expression of bamD gene increased by 2 times. However, the inhibitory effect of 18β-glycyrrhetinic acid on the membrane insertion function of the BAM complex was not observed in the in vitro recombinant system assay, and the cell membrane integrity assay experiments did not reveal any disruption of the E. coli cell membrane by 18β-glycyrrhetinic acid. Conclusions:Using BamA and BamD proteins as targets, a natural product screening method using affinity ultrafiltration combined with HPLC-MS is established. The screening result shows that 18β-glycyrrhetinic acid can interact with BamD and affect the expression of outer membrane proteins in E. coli. Therefore, the screening and experimental procedures established in this study are of good reference value for the screening of novel antimicrobial drugs from other sources targeting outer membrane proteins, and this study also suggests that the selection of the relevant target sites is crucial for the successful screening of the corresponding natural products.

Humans ; China/epidemiology* ; SARS-CoV-2 ; COVID-19

Background and Objectives: Despite advances in wound treatments, chronic diabetic wounds remain a significant medi-cal challenge. Exosomes from mesenchymal stem cells (MSCs) and small molecule activators of nuclear factor erythroid 2–related factor 2 (Nrf2) have emerged as potential therapies for nonhealing diabetic wounds. This study aimed to evaluate the effects of exosomes from bone marrow-derived MSCs (BMSCs) alone, or in combination with a small molecule activator of Nrf2 on diabetic wound healing. Methods: and Results: BMSCs and endothelial progenitor cells (EPCs) were isolated from the femur and tibia bone marrow of Sprague-Dawley (SD) rats and culture-expanded. Exosomes were harvested from the BMSC culture supernatants through ultracentrifugation. The effects of the exosomes and Nrf2 knockdown, alone or in combination, on EPC tube formation were evaluated. Streptozotocin-induced diabetic rats bearing a fresh full-thickness round wound were treated with the exosomes alone, or in combination with a lentiviral shRNA targeting Nrf2 (Lenti-sh-Nrf2) or tert-butylhydroquinone (tBHQ), a small molecule activator of Nrf2. Two weeks later, wound closure, re-epithelization, collagen deposition, neovascularization, and local inflammation were evaluated. BMSC exosomes promoted while Nrf2 knockdown inhibited EPC tube formation. BMSC exosomes accelerated wound closure, re-epithelization, collagen deposition, and neovascularization, and reduced wound inflammation in diabetic rats. These regenerative and anti-inflammatory effects of the exosomes were inhibited by Lenti-sh-Nrf2 but enhanced by tBHQ administration. Conclusions BMSC exosomes in combination with a small molecule Nrf2 activator hold promise as a new therapeutic option for chronic diabetic wounds.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.

Incidence of acute closed Achilles tendon rupture is high in clinic. Accurate diagnosis of this injury depends on a combination of physical signs and imaging examinations. Although conservative and surgical interventions are common for acute closed Achilles tendon rupture, its optimal treatment remains controversial. This literature review focuses on the research progress concerning this injury so as to analyze its risk factors, diagnostic methods, treatments, early functional rehabilitation, postoperative complications and prognosis evaluation.