Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Profiling and identification of aqueous extract of Cordyceps sinensis by ultra-high performance liquid chromatography tandem quadrupole-orbitrap mass spectrometry / 中国天然药物

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

Prospective comparison of hybrid capture 2 and SPF₁₀-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China / 부인종양

OBJECTIVE: To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers. METHODS: Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF₁₀-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible human papillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed. RESULTS: The overall agreement between HC2 and SPF₁₀-LiPA for detecting carcinogenic HPV was 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positive and LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%–27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%; 95% CI=8.57%–11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95% CI=2.44%–2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%–1.92%) women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was 8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54. CONCLUSION: The noticeable high risk of CIN2+ in women infected with cross-reacted non-carcinogenic HPV and low risk in those with miss-to-detective carcinogenic HPV supported an overall good clinical performance of HC2 for a general cervical cancer screening.

Inhibition of Re Du Ning Injection on Enzyme Activities of Rat Liver Microsomes Using Cocktail Method / 中草药·英文版

Objective Re Du Ning Injection (RDN), a Chinese materia medica injection, is made from the extracts of Lonicerae Japonicae Flos, Gardeniae Fructus, and Artemisiae Annuae Herba. Since last decade, RDN has been widely used in China for the treatment of viral infection, fever, and inflammation. To assess the potential interacting of RDN with co-administered drugs, the inhibitory effects of RDN on the enzyme activities (CYP1A1, CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2) of rat liver microsomes were investigated by a cocktail method. Methods A sensitive and specific LC-MS method capable of simultaneous quantification of five metabolites in rat liver microsomes was developed and validated. Then RDN (0.625%–1.0%) was incubated with rat liver microsomes and specific substrates. The enzyme activities were expressed as the formation rate of the specific metabolites of the substrates (pmol · mg · protein−1 · min−1). Results RDN competitively inhibited the activities of CYP1A2 and CYP2C11, with inhibition constant (Ki) values determined to be 0.18% and 0.63%, respectively. RDN exhibited the mixed inhibition on the activity of CYP2D1, with a Ki value of 0.15%. The activities of CYP1A1 and CYP3A1/2 were not markedly inhibited even by 1.0% RDN. Conclusion RDN could inhibit the rat enzyme activities of CYP1A2, 2C11, and 2D1 in vitro with different inhibition modes, which is worthy of promoting safety and efficacy of RDN.

Measurement of mass fraction of Sanjie Zhentong capsules with near infrared reflectance spectroscopy / 中国中药杂志

Sanjie Zhentong capsules were scanned by using a near infrared spectra probe with different drug mass fraction and the spectral information of capsule shells and contents in it were obtained. Then partial least squares (PLS) models were developed for the prediction of mass fraction of Fritillariae Thunbergii Bulbus and Resine draconis in Sanjie Zhentong capsules. The correlation coefficient (r9c)) and root mean standard error( RMSEC) of 0.949 5, 0.958 2 and 4.742 4, 4.135 7. The models obtained correlation coefficient (r(v)) of 0.919 2, 0.936 7 and root mean square error (RMSECV) of 6.158 9, 5.037 3 respectively in the training set. The paired T test analysis of statistics showed that there were no significant difference between predictive values and measure values. The established models reflected a strong prediction performance and can meet the needs of the production.

Analysis of molecular subtypes and microflora structure of Neisseria meningitidis strains isolated in Jiangxi province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the molecular subtypes and microflora structure of Neisseria meningitidis (Nm) strains isolated in Jiangxi province.</p><p><b>METHODS</b>A total of 123 Nm strains separately isolated from patients, close contacts and health people in 1976-1987 and 2005-2008 were investigated by multilocus sequence typing (MLST) and PorA subtyping, to test the characteristics of gene Nm and sequence porA. Minimum spanning tree was constructed by using BioNumerics software based on data of MLST; and the microflora structure was then analyzed.</p><p><b>RESULTS</b>The serogroups of 67 Nm strains isolated in 1976-1987 included group A (43 strains), group B (18 strains), group C (1 strains) and group W135 (5 strains); while the serogroups of 56 Nm strains isolated in 2005-2008 included group A (3 strains), group B (7 strains), group C (45 strains) and 1 ungrouped strain. The total 123 Nm strains could be divided into 40 MLST types; while the 46 strains in group A could be divided into 14 MLST types, 29 out of which belonged to ST-3 type, accounting for 63.0% (29/46) as the dominant type. All of the 29 strains were isolated between 1976 and 1987, while 14 strains were isolated from patients, 9 were from close contacts and 6 were from health people. The 46 strains in group C could be divided into 5 MLST types, 41 out of which belonged to ST-4821 type, accounting for 89.1% (41/46). All of the strains were isolated between 2005 and 2008, 6 strains were isolated from patients, 6 were from close contacts and 29 were from health people. The porA gene of the total 123 Nm strains were classified to 32 different types, including 24 different VR1 types and 22 different VR2 types. The dominant PorA type of the prevalent strain (ST-3 type, group A) between 1976 and 1987 was P1.7-1, 10, accounting for 39.1% (18/46) of the strains in group A; while the 18 strains were isolated from 11 patients, 4 close contacts and 3 health people. The dominant PorA type of the prevalent strain (ST-4821 type, group C) between 2005 and 2008 was P1.20, 9, accounting for 46.3% (19/41) of the ST-4821 strains in group C; while the 19 strains were isolated from 1 close contacts and 18 health people. P1.7-2, 14 dominated since 2006, including 22 strains, accounting for 53.7% (22/41) of the ST-4821 strains in group C, isolated from 6 patients, 5 close contacts and 11 health people. There were no dominant PorA type found in group B and all the 5 strains in group W135 belonged to ST-174 and the PorA type was P1.21, 16, isolating from 3 close contacts and 2 health people between 1979 and 1980.</p><p><b>CONCLUSION</b>Nm isolated in Jiangxi province showed significant gene polymorphism, as well as predominant lineages existing. In different periods, the prevalent lineages varied a lot, as translating from serogroup A: ST-3:P1.7-1, 10 to serogroup C: ST-4821:P1.7-2, 14 nowadays.</p>

Comparison of protein expression profiles between bortezomib-resistant JurkatB cells with PSMB5 mutation and their parent cells / 中国实验血液学杂志

This study was purposed to investigate the differences of cyto biological characteristics and protein expression levels between bortezomib-resistant T-lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and chemotherapeutic drugs to JurkatB5 cells (end selection concentration of bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and Jurkat cells were analyzed. The cell growth curves were drawn with viable cell counts by trypan blue assay, the colony formation rate were assayed by soft-agar colony culture, and the cell distributions in cell cycle were analyzed by flow cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP and MRP were measured by real-time fluorescence quantitative RT-PCR, the differences of protein expression levels were detected by SpringBio antibody microarray containing 720 proteins. The results showed that the drug resistance multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and JurkatB8 cells did not display significant cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no significant differences in the cell growth curve, colony formation rate and cell distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p > 0.05). There were no significant differences of mRNA expression levels of MDR1, LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable expression points detected by antibody microarray. Among them, 252 protein expression levels were not significantly different between JurkatB5, JurkatB8 and Jurkat cells (< 2-fold), including 15 drug resistance-related proteins. 12 proteins were detected at higher or lower expression levels in JurkatB5 or JurkatB8 cells then that in Jurkat cells (cell division cycle protein 34, cell division cycle protein 37, CD34 Type II, matrix metalloproteinase-2, tenascin, Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic acid receptor β, integrin β-1), but no proteins were detected in JurkatB5 and JurkatB8 cells with higher or lower expression levels than that in Jurkat cells. It is concluded that there are no significant differences in the characteristics of cellular biology between Jurkat and JurkatB with bortezomib-resistant and PSMB5 G322A mutation. There are no significant phenotype change of MDR and overexpression of genes related to MDR in PSMB5 mutated cells. There are no significantly differential expressions of a majority of known proteins related to drug resistance, tumor cells growth, proliferation, apoptosis, malignancy degree, aggressiveness.

Relationship between the absolute lymphocyte count before or after autologous hematopoietic stem cell transplantation and the prognosis in patients with non-Hodgkin's lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship of the absolute lymphocyte count (ALC) before or after autologous hematopoietic stem cell transplantation (AHSCT), and the infused CD34(+) count with the relapse, disease-free survival (DFS), overall survival (OS) in non-Hodgkin's lymphoma (NHL) patients.</p><p><b>METHODS</b>A retrospective analysis of the relationship of the absolute lymphocyte count before (ALC-Pro) or 15 days after (ALC-15) the AHSCT, and the infused CD34(+) cell count with the relapse, DFS, OS of NHL.</p><p><b>RESULTS</b>ALC-Pro and ALC-15 were related to NHL relapse. The patients with high levels of ALC-Pro and ALC-15 had lower relapse rate. By Kaplan-Meier curve and COX multi-variable regression analysis, it was found that both ALC-Pro and ALC-15 were factors associated with the DFS. Patients infused high levels of CD34(+) cells had longer DFS. Patients with high levels of ALC-Pro, ALC-15, CD34(+) counts had longer OS.</p><p><b>CONCLUSION</b>ALC-Pro, ALC-15 and CD34(+) counts were significant in predicting relapse, DFS and OS for patients with NHL.</p>

An analysis of prognostic factors in 80 myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the WHO classification, clinical and hematological features and risk group of International Prognostic Scoring System (IPSS) in patients with myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>The diagnosis and classification of MDS patients were defined according to the WHO classification. The clinical manifestations, hemogram, bone marrow biopsy and prognosis were retrospectively analyzed.</p><p><b>RESULTS</b>The median age at diagnosis of MDS was 47 yrs being younger than that in some foreign reports. The frequency of abnormal karyotype was 35.14% and +8 was the most frequent abnormal karyotype in our study. Eleven of 74 patients transformed into leukemia. Univariate analysis showed that age, chromosome abnormality, percentage of bone marrow blast cells and number of cytopenias were significantly related to prognosis. There was a statistical difference in cum survival rate between IPSS subcategories (P < 0.05) except that between low- and intermediate I-risk subcategory (P > 0.05). There were statistical differences for refractory anemia (RA) vs RA with excess blast (RAEB), refractory cytopenias with multilineage dysplasia (RCMD) vs RAEB and RAEB-I vs RAEB-II (P < 0.05).</p><p><b>CONCLUSIONS</b>There were differences in age of disease onset, distribution of WHO, sub-classification and abnormal karyotype in this cohort of MDS patients as compared with those in Europe and Japan. It is helpful in diagnosis, treatment and prognosis to divide RAEB into RAEB-I and RAEB-II. IPSS was well applicable in Chinese MDS patients.</p>

A clinical observation of fludarabine-containing regimens in the treatment of low grade non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficiency and adverse effect of the fludarabine-containing regimens in the treatment of low grade non-Hodgkin's lymphoma.</p><p><b>METHODS</b>Thirty-two patients with low grade non-Hodgkin's lymphoma consisting of 19 primary one and 13 relapsed or refractory were treated with fludarabine-containing regimens, which included FMD (fludarabine, mitoxantrone and dexamethasone); FMC (fludarabine, cyclophosphamide and mitoxantrone) and FC ( fludarabine and cyclophosphamide).</p><p><b>RESULTS</b>The average course completed in these 32 patients was 4.1 with a complete response rate (CR), partial response rate (PR) and overall response rate (OR) of 65.6%, 18.8% and 84.4% , respectively. There were no significant difference in CR, PR and OR between primary and relapsed or refractory group (71.4%, 21.0%, 92.4% vs. 46.2%, 13.1%, 59.3%, respectively). Myelotoxicity and immunotoxicity was the dominating adverse effects. Ill to IV grade granulocytopenia and thrombocytopenia were observed in 31.3% (10/32) and 9.4% (3/32) of these patients respectively. Infection developed in 7 patients, and two of them died of pulmonary infection. The median follow-up period was 16 months (1-30 months) with 2-year overall-survival rate (OS) and progression-free survival rate (PFS) of 93.8% and 84.4%, respectively. No significant difference was observed between primary and relapsed or refractory group in OS (100% vs. 76.9%) and PFS (94.7% vs. 69.2%).</p><p><b>CONCLUSION</b>Fludarabine-containing regimens is well tolerated and effective in the treatment of low grade non-Hodgkin's lymphoma.</p>

Study on the application of pulsed-field gel electrophoresis regarding infection sources identification during an outbreak of Vibrio cholerae in Jiangxi Province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the correlation between Vibrio cholerae strains isolated from natural enviroment and fishery products and the source of infection during V. cholerae outbreaks.</p><p><b>METHODS</b>Cholera toxin gene was detected by polymerase chain reaction (PCR) amplification. Pulsed-field gel electrophoresis (PFGE) was used to subtype the isolates. Results of PFGE were analyzed and clustered by BioNumerics software (Version 4.0).</p><p><b>RESULTS</b>During the outbreaks, a total number of thirty O139 V. cholerae related serogroups were collected from patients, carriers, sewage and fishery products were identified and proved to be toxigenic. They could be clustered into four PFGE patterns when digested by Not I. These two V. cholerae outbreaks were caused by the same source of infection because of the following reasons: (1) PFGE patterns of the predominant strains isolated from two outbreaks were identical; (2) they were identical to the PFGE patterns of the strains isolated from the green turtle and rana catesbiana which were bought from the same wholesale store.</p><p><b>CONCLUSION</b>Green turtle and rana catesbiana that were contaminated by toxigenic O139 V. cholerae strains seemed to be the source of infection causing the O139 V. cholerae outbreaks in Jiangxi province. Rapid laboratory surveillance and epidemiologic investigation were important in identifying the source of infection during the outbreaks of V. cholera.</p>