[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Methods for controlling and evaluating residual confounding in the association analysis of observational study with a multicenter database].

The observational research based on big data in healthcare has attracted increasing attention, with the control and evaluation of residual confounding being the critical issue that needs to be solved urgently. This review summarized the methods for statistical adjustment and sensitivity analysis of residual confounding in the association analysis with a multicenter database. Based on individual-level data, the residual confounding can be adjusted in each subcenter using methods such as regression discontinuity design, while the pooled estimate can be obtained as a weighted average. Based on the center-level results, the Bayesian Meta-analysis method can adjust the pooled estimates. The sensitivity analysis of residual confounding can also be carried out using center-level data to calculate the E-value, p^(q), T^(r, q) and G^r,q. The abovementioned methods should be selected reasonably according to the requirements for practical applications, advantages, and disadvantages. For example, the use of subcenter individual data for residual confounding adjustment usually needs strict study design and frequent coordination; the Bayesian Meta-analysis is based on some strong assumptions; the interpretation of the results in the sensitivity analysis, such as E-value requires professional judgment to assess the risk of residual confounding. Therefore, the methods for controlling and evaluating residual confounding in association analysis based on multicenter databases still need further development and improvement.

[Metal artifact reduction and clinical verification in oral and maxillofacial region based on deep learning].

Objective: To construct a kind of neural network for eliminating the metal artifacts in CT images by training the generative adversarial networks (GAN) model, so as to provide reference for clinical practice. Methods: The CT data of patients treated in the Department of Radiology, West China Hospital of Stomatology, Sichuan University from January 2017 to June 2022 were collected. A total of 1 000 cases of artifact-free CT data and 620 cases of metal artifact CT data were obtained, including 5 types of metal restorative materials, namely, fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies. Four hundred metal artifact CT data and 1 000 artifact-free CT data were utilized for simulation synthesis, and 1 000 pairs of simulated artifacts and metal images and simulated metal images (200 pairs of each type) were constructed. Under the condition that the data of the five metal artifacts were equal, the entire data set was randomly (computer random) divided into a training set (800 pairs) and a test set (200 pairs). The former was used to train the GAN model, and the latter was used to evaluate the performance of the GAN model. The test set was evaluated quantitatively and the quantitative indexes were root-mean-square error (RMSE) and structural similarity index measure (SSIM). The trained GAN model was employed to eliminate the metal artifacts from the CT data of the remaining 220 clinical cases of metal artifact CT data, and the elimination results were evaluated by two senior attending doctors using the modified LiKert scale. Results: The RMSE values for artifact elimination of fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies in test set were 0.018±0.004, 0.023±0.007, 0.015±0.003, 0.019±0.004, 0.024±0.008, respectively (F=1.29, P=0.274). The SSIM values were 0.963±0.023, 0.961±0.023, 0.965±0.013, 0.958±0.022, 0.957±0.026, respectively (F=2.22, P=0.069). The intra-group correlation coefficient of 2 evaluators was 0.972. For 220 clinical cases, the overall score of the modified LiKert scale was (3.73±1.13), indicating a satisfactory performance. The scores of modified LiKert scale for fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies were (3.68±1.13), (3.67±1.16), (3.97±1.03), (3.83±1.14), (3.33±1.12), respectively (F=1.44, P=0.145). Conclusions: The metal artifact reduction GAN model constructed in this study can effectively remove the interference of metal artifacts and improve the image quality.

[Virtual reconstruction and clinical verification of maxillary defect based on deep learning].

Objective: To construct a virtual reconstruction method including midspan maxillary defects and provide clinical reference by training a generative adversarial network (GAN) model. Methods: The CT data of middle-aged Han patients with oral diseases who visited the Department of Radiology, West China Hospital of Stomatology, Sichuan University from June 2015 to June 2022 were collected, where the CT data of 100 healthy maxilla and 15 maxillary defects (5 simple unilateral defects, 5 unilateral defects involving zygomatic bone, 5 midspan defects) were selected. Mimics was used to create spherical phantom and simulate bone defects around the healthy maxillas, including simple unilateral defects, unilateral defects involving zygomatic bone and midspan defects. The original image was set as the correct reference for the reconstruction: artificial defects paired with the correct reference were divided into training set (n=70), validation set (n=20) and test set (n=10), where the first two were used to train the GAN model, and the test set was used to evaluate the GAN performance. Data from 15 clinical defects were imported into the trained GAN model for reconstruction, with mirroring and GAN-based virtual reconstruction for unilateral clinical defects, and only the latter method was adopted for midspan defects. The reconstruction results were divided into mirror reconstruction group (n=10), unilateral defect GAN reconstruction group (n=10) and midspan defect GAN reconstruction group (n=5). The test set, mirror reconstruction group, and unilateral defect GAN reconstruction group were quantitatively evaluated, whose quantitative indicators were Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95), and the group results were subjected to one-way ANOVA and Tukey test. The test set, mirror reconstruction group, unilateral defect GAN reconstruction group and midspan defect GAN reconstruction group were qualitatively scored, and Kruskal-Wallis test and Bonferroni correction were used for the total score of each group. Results: The total differences in the test set, mirror reconstruction group, unilateral defect GAN reconstruction group DCS (0.891±0.049, 0.721±0.047, 0.778±0.057, respectively) and HD95 [(3.58±1.51), (5.19±1.38), (4.51±1.10) mm, respectively] were statistically significant (F=28.08, P<0.001; F=3.62, P=0.041); among them, the test set DSC was significantly larger than the mirror reconstruction group (P<0.05), and the test set HD95 was significantly less than the mirror reconstruction group (P<0.05). Overall difference in qualitative total scores [8 (1), 6 (2), 6 (2), and 4 (2) points, respectively] in the test set, mirror reconstruction group, unilateral defect GAN reconstruction group, and midspan defect GAN reconstruction group were statistical significance (H=18.13, P<0.001); pairwise comparison showed that the total score of the test set was significantly higher than that of the mirror reconstruction group (P<0.05). Conclusions: The virtual reconstruction method based on GAN proposed in this study has better virtual reconstruction effect of unilateral defect than mirror technique, and can also realize virtual reconstruction of maxillary midspan defect.

[Application value of combined deep inhalation and breath-hold technique guided by four-dimensional CT in preoperative localization of solitary pulmonary nodules].

Objective: To explore the clinical value of four dimensional computed tomography (4 D CT) guided combined with deep inhalation and breath hold (DIBH) technique in the preoperative localization of solitary pulmonary nodules. Methods: The data of a total of 106 patients with solitary pulmonary nodules from March 2018 to May 2021 in the Ningbo First Hospital were collected retrospectively. Among them, there were 26 males and 80 females aged from 21 to 83 (47.4±14.2) years. According to different localization methods, 53 cases were divided into the control group, as the pulmonary nodules were located by CT guided injection of indocyanine green under calm breathing and 53 cases were divided into in the experimental group, as those patients were treated with indocyanine green injection under the guidance of 4 D CT combined with DIBH technology to locate pulmonary nodules. The three-dimensional distance deviation between pulmonary nodules and indocyanine green injection points was compared between the two groups to obtain the accuracy of pulmonary nodule localization. The preoperative positioning time of the two groups was compared by timing. Results: Among the 106 patients, there were 46 pure ground glass nodules, 32 sub solid nodules and 28 solid nodules, all of which were successfully localized before operation, with a success rate of 100%. The size of pulmonary nodules in the control group was (9.1±2.3) mm and the three-dimensional deviation[M(Q1, Q3)]between indocyanine green injection site and pulmonary nodules was X axis [7.0 (3.7, 12.6)] mm, Y axis [6.6 (2.9, 11.2)] mm, Z axis [3.0 (2.0, 6.0)]mm, respectively, and the preoperative positioning time was (11.4±3.8) min. The size of pulmonary nodules in the experimental group was (8.9±2.1) mm, and the deviations in 3 D direction were X axis [4.8 (3.0, 7.9)]mm, Y axis [3.8 (1.3, 7.5)]mm, Z axis [4.0 (2.0, 6.0)] mm, respectively. The preoperative positioning time was (9.3±3.0) min. There were statistically significant differences in preoperative positioning time and deviation of X and Y axis between the experimental group and the control group (P<0.05), but no statistically significant differences was found in deviation of Z axis (P>0.05). Conclusion: 4 D CT guided DIBH technology could improve the accuracy of preoperative localization of pulmonary nodules and save operation time, which is worthy of popularization.

The effect of androgen on wool follicles and keratin production in Hetian sheep / Efeito do androgênio na produção de folículos e queratina em ovinos Hetianos

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

The effect of androgen on wool follicles and keratin production in Hetian sheep.

To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

[A comparison of clinical characteristics between patients with and without"recurrence"RNA positive with COVID-19].

Objective: To analysis the clinical characteristics of"recurrence"RNA positive patients with Coronavirus disease 2019 （COVID-19） and compared with those without"recurrence". Methods: 98 patients with COVID-19 in Wuhan Jinyintan Hospital and designated treatment hospitals in Quanzhou were included in this study from February 2020 to April 2020. There were 55 males and 43 females， aged from15 to 83 years， with a median age of 57.5 years， in which 20 cases were complicated with basic diseases. 15 of these patients had been diagnosed and hospitalized had been found as"recurrence"2019-nCoV RNA positive after discharge while the other 83 cases were all negative. The clinical classification of all patients was common type. Clinical data of the COVID-19 RNA"recurrence"patients were collected， and general situations， symptoms， laboratory examinations and CT images were also observed and analyzed. The patients were divided into 2019-nCoV"recurrent"group and 2019-nCoV"non-recurrent"group. There are 10 males and 5 females in 2019-nCoV"recurrent"group while 45 males and 38 females in"non-recurrent"group （χ²=0.800，P=0.371）. The age of 2019-nCoV"recurrent"group （57±21） was higher than that of"non-recurrent"group（53±17）. 8 of 15 the COVID-19"recurrent"group patients and 12 of 83"non-recurrent"patients have basic diseases. IgG and IgM of 2019-nCoV， IL-6， procalcitonin， ESR， CRP， BNP and other serum biochemical index levels were measured and compared between groups. Results: （1） The proportion of patients with common type of COVID-19 was 15.3% during 2-week medical observation after discharge. （2） All of the 2019-nCoV"recurrent"patients were hospitalized due to COVID-19 RNA positive， when they were quarantined after discharged from hospital. All the patients with mild symptoms which were clarified as common type， including 5 cases of fever， 6 cases of cough， 5 cases of expectoration， and 2 cases of slight shortness of breath. The time of symptoms appeared on （5.73±2.82） days after discharge. （3） The serum procalcitonin of all 2019-nCoV"recurrent"group patients were normal（all<0.05 ng/ml）. The BNP of"recurrent"group （151±171） ng/L， was higher than that of"non-recurrent"group （63±78） ng/L （t = 3.207， P = 0.000）. There was no significant difference in laboratory tests like leukocyte ［（6.17±2.4） and （6.04±2.41）×109/L］， lymphocyte［（1.59±0.52） and （1.32±0.64）×109/L］， CRP ［（12.54±28.20） and （21.74±25.63）mg/L］， ESR ［（31.07±28.72） and （34.10±22.16）mm/1 h］， AST ［（24.73±9.15） and （30.24±23.20）U/L］， ALT ［（22.60±12.82） and （36.47±34.12）U/L）， LDH ［（268±208） and （270±164）U/L］， D-dimer ［（0.60±0.50） and （0.84±0.98）µg/L］， ferritin ［（294±195） and （395±319）µg/L］， IL-6 ［（9.17±6.42） and （14.28±17.74）ng/Lï¼½ and BUN （5.77±2.66） and （4.74±2.81）U/Lï¼½ between"recurrent"and"non-recurrent"groups （all P>0.05）. （4） In"recurrent"group， ground glass， exudative or solid lesions could be found in most of the chest CT performed on re-admission. Meanwhile， fibrosis lesion was relatively rare. （5） There were no secondary transmissions were found to be caused by the 2019-nCoV"recurrent"group patients. Conclusions: Most of the 2019-nCoV patients had underlying diseases and active lesions were still found in CT images， so the possibility of virus replication may still exist. All"recurrent"patients had mild illness which may suggest that they were in recovery stage, and no evidence of transmission is found.

[Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage â a1 （LVSI+）-â b1 cervical cancer patients with different tumor size: a big database in China].

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

[Research progress on abnormal liver function in pregnancy].

Abnormal liver function in pregnancy is a common clinical problem in the department of obstetrics and liver disease, but its severity can cause danger to the life of the mother and fetus. Therefore, the different cause of abnormal liver function in pregnancy should be assessed accurately in order to take early intervention measures. Moreover, it is necessary to comprehensively evaluate the situation of both mother and fetus to obtain the optimal treatment effect for abnormal liver function caused by different types of pregnancy-related liver diseases.

[Clinical control status and quality of life in patients with chronic rhinosinusitis and asthma after endoscopic surgery].

Objective:The aim of this study is to investigate the clinical control status and quality of life of patients with chronic sinusitis and asthma after endoscopic surgery. Method:A prospective study of 36 patients with chronic rhinosinusitis and asthma who had endoscopic surgery. All patients underwent standardized drug therapy before operation. After evaluation by the respiratory and anesthesiologists, they were admitted to the hospital for endoscopic surgery. The patients were closely monitored during the operation, and the patients were observed and recorded. Self-control was performed to compare the observational indexes of the patients for half a year and one year after surgery. Result:①The Asthma Control Scale （ACT） score showed that the proportion of complete control of asthma increased from 8.33% before surgery to 30.56% in the first half of the year and 27.78% in 1 year, which was significantly improved （P<0.05）. ②Asthma Quality of Life Questionnaire（AQLQ） showedthatthe indicators of postoperative quality except the response to the stimulus, limited activity, asthma symptoms, psychological status and concern for their own health are all have statistically significant （P<0.05）. ③In the first half of the year, there were 47.22%, in 1 year, 41.67% of the patients had improved asthma medication. There was no difference between the two groups （P>0.05）. ④The exhaled nitric oxide index was decreased in the first half of the year and in the first year after operation. ⑤There was no significant change in lung function indexes before and after operation （P>0.05）. Conclusion:In patients with chronic sinusitis and asthma, under the comprehensive treatment of endoscopic surgery, improving the quality of life of patients can also improve the control of asthma symptoms and medication, control the development of asthma, and have a positive effect on clinical efficacy.

Oxidative stress induces B lymphocyte DNA damage and apoptosis by upregulating p66shc.

OBJECTIVE: B lymphoma is a type of malignant tumor originating from the lymphatic hematopoietic system. The pathogenesis and treatment methods are not clear. The change of oxidative stress is closely related to the cell DNA damage and cell apoptosis, which may be served as a target for cancer treatment. This study aims to illustrate the role of oxidative stress in the regulation of B lymphocytoma. PATIENTS AND METHODS: The tumor tissue was collected from patients with B lymphocytoma. The p66shc level was detected by Western blot. Hydrogen peroxide (H2O2) was assessed by the kit. The oxidative stress model of B lymphoma cell was established by H2O2 treatment. ROS inhibitor or RNAi was used to regulate ROS level. ROS level was determined by flow cytometry. 8-OHdG level (DNA damage product) was tested by the kit. Cell apoptosis was evaluated by annexin V-PI. RESULTS: P66shc expression was significantly reduced, while H2O2 production was significantly decreased in the tumor tissue of B lymphoma compared with adjacent normal control. H2O2 stimulation markedly elevated ROS level and p66shc expression (p < 0.05), accompanied by the aggravation of DNA damage and increase of apoptosis. ROS inhibitor or p66shc RNAi treatment significantly attenuated DNA damage and declined cell apoptosis (p < 0.05). CONCLUSIONS: ROS production promoted p66shc expression, induced DNA damage, and facilitated cell apoptosis. Upregulation of p66shc by oxidative stress could be treated as a new therapeutic target for B lymphoma.

Synergistic effects of chlorambucil and TRAIL on apoptosis and proliferation of Raji cells.

OBJECTIVE: Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) can induce the apoptosis of tumor cells, but leaving its effect on malignant lymphoma largely insignificant, as these tumors may develop drug resistance. Chlorambucil (CLB) had definitive treatment efficacy on low-malignant non-Hodgkin lymphoma (NHL), but with unclear efficacy on highly malignant Burkitt lymphoma. A study has been shown that CLB could enhance the sensitivity of chronic lymphatic leukemia cells against TRAIL. This work aims to investigate the effect of CLB combined with TRAIL on in vitro proliferation and apoptosis of Raji cells. MATERIALS AND METHODS: TRAIL (0, 20, 40 and 80 ng/ml) or CLB (0, 2.5 5 and 10 µM) was used to treat Raji cells. Cell counting kit 8 (CCK-8) was used to test proliferation whilst flow cytometry was employed to examine the apoptosis. The effect of TRAIL or CLB treatment on expression of death receptor 4 (DR4) and DR5 was tested. Combined treatment (80 ng/ml TRAIL and 10 µM CLB) was adopted for observing Raji cell proliferation and apoptosis. RESULTS: Single treatment of TRAIL or CLB has weak effects of inducing apoptosis or inhibiting proliferation. TRAIL concentration has no significant effects on DR4/DR5 expression in Raji cells, whilst CLB treatment elevated those gene expressions. Combined treatment of TRAIL and CLB had more potent effects regarding cell proliferation inhibition or apoptosis induction compared to single treatment. CONCLUSIONS: TRAIL or CLB has weak inhibitor effects on Raji cell proliferation or induction of apoptosis. Via up-regulating DR4 and DR5 expression, CLB has synergistic effects with TRAIL to potentiate the apoptotic induction and proliferation inhibition role.

[Oncolytic property of HSV-1 recombinant viruses carrying the human IL-12].

Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL-12, and investigate the virus' replication ability and oncolytic property in vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome technology.The replication ability and the efficiency of inhibiting tumor were detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and MH1006 respectively.The murine tumor model was established by subcutaneous inoculation Neuro-2a cells on both sides of mice back respectively.A dosage of 2×10(6) PFU of HSV-wt, MH1001(recombinant HSV-1 deleted IR), MH1005, MH1006 and Mock were injected 3 times intratumorally on one side of mice back in every 3 days, the tumor volume and survival rate of the mice were measured. Results: The replication abilities of MH1005, MH1006 and HSV-wt in 293FT cells were insignificant (P>0.05); the replication abilities of recombinant HSV-1 in G422 and Neuro-2a were higher than that in SK-N-SH; and the nerve tumor cells could be inhibited significantly by recombinant HSV-1.After 15 days of treatment, on the mouse backside with injection treatment, the tumor volumes of group HSV-wt (6 267±484), MH1001 (5 730±1 071), MH1005 (4 537±538)and MH1006 (4 150±476)mm(3) were smaller than that of group Mock (6 957±722) mm(3) significantly (all P<0.01); on the mouse backside without injection treatment, the tumor volumes of group MH1005 (5 952±607) and MH1006 (5 473±661) mm(3) were smaller than those of HSV-wt (6 785±1 063), MH1001 (6 774±808) and Mock (6 957±190) mm(3) significantly (all P<0.05); after 35 days of treatment, the mice survival rates of group MH1005 (100%) and MH1006 (100%) were higher than those of MH1001 (67%), HSV-wt (50%) and Mock (33%) significantly (all P<0.05). Conclusion: MH1005 and MH1006 can infect nerve tumor cells and replicate at high level, the viruses not only kill tumor cells directly but also induce immunological rejection to tumor, and prolong the survival of mice bearing tumor.

Effect of phospholipid composition on characterization of liposomes containing 9-nitrocamptothecin.

9-Nitrocamptothecin (9-NC), a newly developed camptothecin derivative, had poor solubility in any pharmaceutically acceptable solvents. One way of improving the solubility is to formulate the drug into liposomes. However, 9-NC has low affinity to lipid membranes resulting in a very low drug-to-liposome entrapment. We developed a novel liposome-based 9-NC formulation which was composed of soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), and cholesterol. Compared with conventional liposomes composed of only SPC and cholesterol, 9-NC/lipid molar ratio increased from 1:72 to 1:18 while incorporation efficiency was still maintained about 80%. In addition, after 9-NC was encapsulated into novel liposomes, pharmacokinetic results revealed an increase in area under the plasma concentration-time curve (AUC) and a decrease in distribution volume of 9-NC following intravenous administration to rats. Increased stability in plasma may account for the improved pharmacokinetic behavior of the novel liposomes. Effect of HSPC/SPC molar ratio on characterization of the novel liposomes was also investigated. Except for drug/lipid molar ratio and encapsulation efficiency, HSPC/SPC molar ratio had only a little effect on other properties of novel liposomes. In conclusion, the study suggests that the novel liposomes can act as promising carriers for hydrophobic substances such as 9-NC.

Cysticercosis in Domestic Animals and Rodents / 中国人兽共患病学报

Cysticercus cellulosae, C. bovis, and C. taiwanensis are the three species of cysticercosis of human taeniid with their adults worms Taenia solium, T. saginata saginata and T. s. asiatica respectively. C. cellulosae is prevalent in America, Europe and Asia, C. bovis in Africa, America and Asia and C. taiwanensis in Asia. The natural infection source is pig for C. cellulosae, cattle for C. bovis and pig and wild boar for C. taiwanensis. The predilection sites are muscles for C. cellulosae and C. bovis and liver for C. taiwanensis. While the prepatent periods of these three species were 60-70 days, 60-75 days and 28 days respectively. Most C. cellulosae and a few for C. bovis and C. taiwanensis survive in pig, while most C. bovis and a few for C. taiwanensis survive in cattle. In rodent, all three species have a long life. C. cellulosae and C. bovis migrate through blood and lymph vessels to the small intestinal wall and then to the body muscles while C. taiwanensis migrate through blood vessels to the small intestinal wall and then to the liver. The minimal effective dosage of praziquantel against cysticercosis should be 100 mg/kg daily for three consecutive days.

Efficacy and safety of telmisartan vs. losartan in control of mild-to-moderate hypertension: a multicentre, randomised, double-blind study.

This multicentre, randomised, double-blind, double-dummy, parallel-group study compared the efficacy and safety of telmisartan with those of losartan after 8 weeks' treatment. In total, 330 patients with mild-to-moderate hypertension (systolic blood pressure [SBP] <180 mmHg; diastolic blood pressure [DBP] 95-109 mmHg) were randomly assigned to receive once-daily treatment with telmisartan 40 mg (n = 164) or losartan 50 mg (n = 166). After 4 weeks' treatment, if a patient's DBP was > or = 90 mmHg, the dose was increased to telmisartan 80 mg or losartan 100 mg, respectively. The results show that mean trough seated blood pressure was reduced significantly more in the telmisartan group than that in the losartan group (SBP 12.5 mmHg vs. 9.4 mmHg, p = 0.037; DBP 10.9 mmHg vs. 9.3 mmHg, p = 0.030). The overall DBP response rate (reduction from baseline in mean seated DBP > or = 10 mmHg and/or a mean seated DBP <90 mmHg) at the end of the study in the telmisartan group was higher than that in losartan group (70.1% vs. 58.7%, p = 0.020). At both the low and high doses, the DBP response rates for telmisartan were significantly higher than those for losartan (telmisartan 40 mg vs. losartan 50 mg: 46.3% vs. 32.5%, p = 0.010; telmisartan 80 mg vs. losartan 100 mg: 79.3% vs. 65.3%, p = 0.008). Adverse events with the two treatments were comparable (telmisartan vs. losartan 23.2% vs. 22.9%, p = 0.952). Most events were mild in intensity and abated within 72 h. Thus, telmisartan 40 mg or 80 mg administered once daily can reduce SBP and DBP effectively and safely.

Experimental studies on small hooks preceding large hooks in the growth and development of Taenia solium metacestodes.

In the present study, we have determined the growth and development pattern of rostellar hooklets of Taenia solium cysticerci (Zhengzhou and Harbin strains) in three pigs (1 SEM and 2 L-SEM strains) 89-196 days post experimental infection. A total of 3,675 cysticerci were collected from 3 pigs, 3,007 (82%) of 3,675 cysticerci were evaginated by enzyme method. 439 (15%) evaginated cysticerci were carefully examined and measured after dehydration, staining, and mounting on microscopic slides. Among 439 cysticerci, 234 (53%) had pair rostellar hooks, 88 (20%) with unpair hooks, 60 (14%) only small (outer row) hooks, and 57 (13%) no hooks including 34 hooks were completely dropped and 23 no hooks developed. The number ranged from 10 to 17 pairs for pair hooks and 1 to 29 for unpair ones. The length and width of rostallar hooks on the scolex of cysticerci were usually larger in the pig with longer infection time. Moreover, cysticerci with pair and unpair rostellar hooks had only small hooks and no hooks were present on their scolices. However, cysticerci with only large (inner row) hooks were not found. These findings indicate that the growth and development of small hooks precedes that of the large hooks in the formation of the two-row pattern rostellar hook in Cysticercus cellulosae.

[Transdermal delivery of cyclosporin A solubilized in mixed micelles through mice skin].

AIM: To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS: When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate-phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS: In vitro, mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X-100 > Tween-20. In vivo, peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION: Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.