Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To explore the feasibility of smart phone real-time picture exchange-assisted telecytopathology for rapid on-site evaluation (tele-ROSE), and the role of tele-ROSE in improving the diagnostic efficiency of endoscopic physicians.Methods:Data of patients who underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) from April 2020 to May 2021 in Qilu Hospital of Shandong University were retrospectively collected. Patients who didn't receive ROSE from April 2020 to October 2020 were enrolled in the non-ROSE group, and those who underwent ROSE from November 2020 to May 2021 were enrolled in the ROSE group, of which endosonographers used WeChat on the smartphone to send ROSE images to cytopathologists from November 2020 to March 2021 were the mobile phone group, and those whose ROSE results independently diagnosed by trained endosonographers from April 2021 to May 2021 were the self-ROSE group. Basic information, ROSE results, postoperative pathology and follow-up were compared, and the diagnostic effectiveness of tele-ROSE was analyzed.Results:A total of 188 cases were included, of which 179 cases (95.2%) were solid pancreatic lesions and 9 (4.8%) were enterocoelia lesions. There was no significant difference in the puncture time among the non-ROSE, mobile phone and self-ROSE groups [3 (3, 4) VS 3 (3, 4) VS 3 (2, 4), H=1.320, P=0.517]. With the final diagnosis as the golden standard, the sensitivity, the specificity, the accuracy, the positive predictive value, the negative predictive value and Kappa value of the non-ROSE group were 80.6% (58/72), 89.5% (17/19), 82.4% (75/91), 96.7% (58/60), 54.8% (17/31), and 0.6 respectively. The corresponding indices in the ROSE group were 97.4% (74/76), 100.0% (21/21), 97.9% (95/97), 100.0% (74/74), 91.3% (21/23), and 0.9 respectively, those of the mobile phone group were 95.2% (40/42), 100.0% (10/10), 96.2% (50/52), 100.0% (40/40), 83.3% (10/12), and 0.9 respcetively, and those of the self-ROSE group were 100.0% (34/34), 100.0% (11/11), 100.0% (45/45), 100.0% (34/34), 100.0% (11/11), and 1.0 respectively. The sensitivity ( P=0.002), the accuracy ( P=0.001) and the negative predictive value ( P=0.009) of the ROSE group were significantly higher than those of the non-ROSE group, and there was no significant difference in other diagnostic efficacy indices ( P>0.05). There was no significant difference between the mobile phone group and the self-ROSE group in diagnostic efficacy ( P>0.05). Conclusion:Instant smartphone-assisted tele-ROSE through WeChat can well meet the needs of pathologists and endoscopic physicians. After the application of tele-ROSE training, the diagnostic accuracy of endoscopic physicians is equivalent to that of cytopathologist, which helps to obtain more sufficient specimens under endoscopy and improve the diagnostic accuracy of EUS-FNA.

ObjectiveTo determine the genomic characteristics of a subgenus B human adenovirus strain isolated in Shanghai in 2021. MethodsAn adenovirus type 55 strain was isolated and identified from a patient with acute hemorrhagic conjunctivitis （AHC）. Complete genome of the strain was obtained using the next-generation sequencing （NGS）. Phylogenetic trees were reconstructed based on the sequences of Hexon， Fiber， Penton and complete genome to genomically characterize this strain. ResultsPhylogenetic analysis based on the complete genome classified this strain （MH2021001） into subgenus B， subspecies B2 of HAdV-55. Hexon gene of MH2021001 had close phylogenetic relationship with HAdV-11， while Fiber and Penton genes had close relationship with HAdV-14. The MH2021001 showed high nucleotide identity with currently prevalent HAdV⁃55 strains （>99.90%）. The complete genome had 99.96% nucleotide identity to the 73-GD_CHN_2016 strain isolated in Guangdong. In addition， the amino acid sequence of MH2021001 had several substitutions in regions coding for E1B， L4， E3 and L5. ConclusionThis strain has been classified to HAdV-B55. No recombination event is identified in the complete genome. Due to multiple amino acid substitutions， the biological characteristics of the strain need to be further identified.

Objective: : Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. Methods: : A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. Results: : Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). Conclusion : Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.

OBJECTIVE To analyze the effects of the national centralized drug procurement （NCDP） policy on drug availability and the structure of drug use in public hospitals. METHODS Using hypoglycemic， lipid-lowering， antiviral drugs， and psychiatric drugs for the treatment of mental illness and depression as objects， the interrupted time series model was used to quantitatively evaluate the changes in consumption sum of drugs， consumption amount and daily cost of the target drugs in national sample hospitals as well as the changes in per capita medication frequency， outpatient prescription amount， and medical insurance surplus of target drugs in a third grade class A hospital before and after the implementation of NCDP policy. RESULTS After the implementation of the NCDP policy， the volume for the four bid-winning drugs increased significantly （P＜0.01 for the remaining three categories except for hypoglycemic drugs）， but DDDc （P＜0.01） and the amount of related drugs （P＜0.001） decreased significantly. The volume for the non-winning drugs （except for lipid-lowering drugs） decreased significantly （P＜0.05）， and DDDc also decreased significantly （P＜0.05 for other 3 categories except for psychiatric drugs）； the volume （P＜0.01） and DDDc （P＜0.01 only for psychiatric drugs） for alternative drugs all increased except for antiviral drugs. The structure of drug use for different drugs was affected differently by the NCDP policy，and that of hypoglycemic drugs was affected obviously； the proportion of alternative drugs increased after centralized procurement. The outpatient prescription amount of each hospital significantly decreased after centralized procurement，and the decrease in the cost paid by the patients using lipid-lowering and antiviral drugs related to centralized procurement was greater than 0.60； the remaining medical insurance amount for bid-winning drugs was approximately 1.252 5 million yuan. CONCLUSIONS NCDP policy effectively alleviates the burden of medical expenditure and also drives the structure changes of drug use such as the substitution of generic drugs for original drugs， the growth of the volume of alternative drugs.

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Objective:To explore the expression features of cytochrome C oxidase subunit Ⅰ (MT-CO1), BCL2 interacting protein 3 (BNIP3) and interleukin (IL)-1β in the liver of MRL/lpr lupus mice.Methods:The mRNA and protein levels of MT-CO1, BNIP3, IL-1β, p16 and p21 in lupus mice and control mice were detected by polymerase chain reaction (PCR) and Western blot, the IL-1β expression site were detected by hematoxylin and eosin (HE) staining and immunohistochemical method, and themalondialdehyde (MDA) was detected by colorimetry. Hepatocytes and macrophages were stimulated with lipopolysaccharide (LPS), while hepatocytes were also cultured with supernatants obtained after macrophages stimulated with LPS, and the mRNA and protein levels of MT-CO1, BNIP3 and LC3B, as well as p16 and p21 expression, were determined by qPCR and Western blot. The expression of mitochondrial reactive oxygen species (mtROS) was detected by immunofluorescence. One way Analysis of Variance (ANOVA) was used to compare the mean of each group, and LSD method was used to compare the means of multiple samples, and Tamhane's T2 method was used to compare the means of multiple samples when the variance was uniform. Results:The results of PCR showed that the mRNA levels of MT-CO1 and BNIP3 in the liver tissue of the lupus group (0.14±0.04; 0.16±0.05) were significantly lower than those of the control group (0.11±0.04; 0.16±0.06), and the differences were statistically significant ( t=7.16, P<0.001; t=4.54, P<0.001). The expression levels of IL-1β, p16 and p21 in the lupus group (2.06±0.69; 0.37±0.14; 0.16±0.06) were significantly higher than those of the control group (0.23±0.06; 0.25±0.08; 0.11±0.04) ( t=9.58, P<0.001; t=24.35, P<0.001; t=22.36, P<0.001). The results of Western blot were consistent with those of PCR. HE staining showed lymphocyte infiltration in the liver tissue of lupus mice, and immunohistochemistry showed IL-1β in the liver tissue of lupus mice. The positive cells were mainly concentrated in the sinusoids, and the expression of hepatic parenchymal cells was not rearkable. The content of MDA in liver tissue of the lupus group (0.19±0.10) was higher than that of the control group (0.17±0.09), and the difference was statistically significant ( t=4.33, P=0.005). LPS directly stimulated AML12 hepatocytes (0.069±0.028; 0.17±0.07). The PCR results showed that compared with the control group (0.176±0.072; 0.08±0.03), the expression of MT-CO1, and BNIP3 were not significantly different ( t=1.01, P=0.337; t=0.88, P=0.399). The expression of IL-1β was significantly higher when incubated with the supernatants of LPS stimulated macrophages (0.28±0.09) compared than that of the control group (0.15±0.05) ( t=28.26, P<0.001). The results of PCR showed that the mRNA levels of MT-CO1 and BNIP3 in the LPS stimulated group (0.046±0.026; 0.17±0.05) were significantly lower than those in the control group (0.143±0.083; 0.18±0.06), and the differences were statistically significant ( t=7.52, P<0.001; t=4.24, P<0.001), The expression of p16 and p21 in LPS stimulated group (0.29±0.09; 0.27±0.09) were significantly higher than those in the control group (0.18±0.06; 0.22±0.07) ( t=13.54, P<0.001; t=8.69, P<0.001). The results of Western blot were consistent with those of PCR. Immunofluorescence showed that the fluorescence intensity of mtROS in LPS stimulated group (0.25±0.10) was higher than that in the control group (0.08±0.03), and the difference was statistically significant ( t= 4.86, P<0.001). Conclusion:Immune-mediated inflammation in the liver tissue of lupus mice can stimulate liver parenchymal cells to cause intracellular mitochondrial dysfunction. However, the mechanism of liver organ damage in lupus mice is not limited to the immune-mediated inflammation of immune active cells, but also include parenchymal cell mitochondrial dysfunction.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

Objective: To investigate the risk factors affecting the occurrence of complications in patients with vaginal bleeding after in vitro fertilization/intracytoplasmic sperm injection embryo transfer(IVF/ICSI-ET) and the construction of nomogram prediction model. Methods: A total of 272 patients with threatened abortion after IVF/ICSI-ET were retrospectively analyzed in this study. They were divided into the live birth group and abortion group according to the final outcome of pregnancy. Patient characteristics were evaluated using the chi-square test, independent-samples Student's t-test or Wilcoxon rank sum test. A nomogram was created to predict the pregnancy outcome of women with threatened abortion who received IVF/ICSI using multivariate logistic regression coefficients. Results: There was no significant difference in the basic data, percentage of frozen embryos, treatment method, number of embryos transferred, high-quality embryo rate, and embryo implantation rate of the live birth group and abortion group(P>0.05). There were significant differences in body mass index, the onset of vaginal bleeding time after transplantation, serum levels of hCG and progesterone on 14 th day after embryo-transfer, and the number of gestational sacs between the two groups(P<0.05). After multivariate logistic regression analysis, the onset of vaginal bleeding time after transplantation and serum hCG levels on 14 th day after transfer were statistically significant(P<0.05). The nomogram was established based on the above indicators, with an area under the curve of 0.710 for the nomogram. The area under the ROC curve of our nomogram was better than the area under the ROC curve of a single risk factor(AUC of bleeding time after embryo-transfer: 0.644, AUC of serum hCG14:0.625). Conclusion The nomogram model established based on the onset of vaginal bleeding time after embryo-transfer and serum hCG value on 14 th day after embryo-transfer can better predict pregnancy outcome of patients with threatened abortion after IVF/ICSI-ET.