[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.

[Clinical analysis of 4 children with cryptogenic organizing pneumonia].

Objective: To analyze the clinical features of children with cryptogenic organizing pneumonia (COP) confirmed by pathology. Methods: The clinical manifestations, imaging, pathology, treatment and outcome data of 4 children with COP confirmed by thoracoscopic lung biopsy were retrospectively analyzed, who were hospitalized at Respiratory Department of Shenzhen Children's Hospital from January 2004 to December 2022. Results: All of the 4 patients were male, the age ranged from 1 year 3 months to 14 years. The time from onset to diagnosis was 3 months to 3 years. The follow-up duration was 6 months to 6 years. All the 4 cases had cough, 2 cases had tachypnea and wheezing, 1 case had expectoration, 1 case had chest pain, 1 case had decreased activity tolerance and weight loss. Rales in 2 cases and hypoxemia in 1 case. Pulmonary high resolution CT showed diffuse distribution, involvement of both lungs in 3 cases, and single lung combined migration in 1 case.Three cases showed ground-glass opacity, consolidation, patchy or fibrous strips, and 1 case presented air bronchogram and "reversed halo sign". All the 4 cases were performed thoracoscopic lung biopsy, and the pathological findings showed cellulose exudate or small nodules filled with granulation tissue or fibroblasts in the alveolar cavity and small airways, and 1 case was Masson corpuscle positive. Three patients achieved remission after glucocorticoid therapy. Spontaneous remission without treatment was seen in 1 patient.Two cases were followed up for 17 months and 6 years, respectively, who had excellent outcome. Conclusions: The manifestations of COP in children include cough, expectoration and chest pain. Infants and young children may have tachypnea and wheezing. The most common chest CT findings are diffuse distribution of ground-glass opacity, patchy and consolidation in both lungs. Diagnosis should depend on pathological examination. The effect of glucocorticoid therapy is good.

[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.

[Analysis of the current status and related factors of human papillomavirus infection among community-dwelling women aged 18-24 years without a history of vaccination in Shanghai City].

Objective: To understand the status of human papillomavirus (HPV) infection among young women without a history of vaccination in Shanghai, and analyze the related factors of HPV infection in this population. Methods: A total of 2 660 women aged 18-24 years old who had made an appointment for HPV vaccine at 36 community health service centers in Shanghai from July 2022 to February 2023 were selected as the study subjects. Basic information (including demographic characteristics, previous disease history, female menstrual and reproductive history, sexual life history, etc.) was collected by a self-filling electronic questionnaire. Cervical secretions were detected by HPV nucleic acid typing. The multivariate logistic regression model was used to analyze the factors related to high-risk HPV (HR-HPV) infection in the target population. Results: The age of the subjects was (23±1) years old, and the infection rate of HPV was 14.51% (386 cases), among which the infection rates of HR-HPV and low-risk HPV were 13.53% (360 cases) and 1.84% (49 cases), respectively. The main subtypes of HR-HPV infection were HPV52, 16, 58, 39 and 66. The multivariate logistic regression model analysis showed that compared with the control group, the OR (95%CI) values for HR-HPV infection in the group of married, earned less than 2 000 yuan/month, drank alcohol occasionally, gynecological disease history, had two or more sexual partners in the past year, and did not know whether the partners had other sexual partners were 0.41 (0.25-0.66), 0.39 (0.21-0.70), 1.45 (1.13-1.86), 1.29 (1.00-1.66), 2.18-5.18 (1.02-16.05), and 1.82 (1.31-2.54), respectively. Conclusion: The infection rate of HPV among women aged 18-24 years old in Shanghai remains at a high level. The main subtypes of HR-HPV infection are HPV52, 16, 58, 39 and 66. The marital status, economic income level, drinking status, gynecological disease history and sexual life history are related to HR-HPV infection.

[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].

Objective: To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. Methods: A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ2 test was used for categorical variables. Results: A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ2=6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ²=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ2=4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×109/L vs. 10.5 (2.5-32.2)×109/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) µg/L vs. 0.24 (0.01-18.85) µg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions: The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

[Consistency of peripheral whole blood and venous serum procalcitonin in children: a multicenter parallel controlled study].

Objective: To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection. Methods: This multicenter cross-sectional parallel control study was conducted in 11 children's hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman's rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection. Results: A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum (r=0.97, P<0.01). The linear regression equation was PCTvenous serum=0.135+0.929×PCTperipheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods (r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 µg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 µg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 µg/L, respectively. Conclusions: There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

[Clinical study of cell sheets containing allogeneic keratinocytes and fibroblasts for the treatment of partial-thickness burn wounds].

Objective: To evaluate the efficacy and safety of cell sheets containing allogeneic keratinocytes and fibroblasts in the treatment of partial-thickness burn wounds. Methods: The cell sheets containing allogeneic keratinocytes and fibroblasts were constructed using polyurethane biofilm as carrier. Then gross observation and histological observation were conducted. From April 2016 to December 2017, Changhai Hospital of Naval Medical University recruited patients with acute partial-thickness burn wounds that met the inclusion criteria for this prospective and positively self-controlled clinical trial. Recruitment of 40 acute partial-thickness burn wounds were planned with each selected single wound being not smaller than 10 cm×10 cm and not more than 5% total body surface area (TBSA). Each wound was equally divided into two areas, which were recruited into cell sheet group and conventional treatment group according to the random number table. The wounds in cell sheet group were covered by cell sheet and then sterile gauze as secondary dressings. Depending on the wound healing and exudation, the sterile gauze was replaced every 1 to 3 day (s) after the treatment was started, and the cell sheet was replaced every 7 days (namely dressing changing). The wounds in conventional treatment group were covered by sulfadiazine silver cream gauze and then dressed with sterile gauze, with the dressings changed every 2 to 3 days depending on wound exudation. On treatment day 5, 7, 10, and 14, the wound healing rates in the two groups were calculated. The complete wound healing time, the total number of dressing changes, and the status of wound infection during treatment were recorded. The Visual Analogue Scale was used to score the pain at the first dressing change. Scar formation of patients was followed up for 6 to 12 months after injury. Safety indicators including vital signs, laboratory examination indexes, and adverse reactions during treatment were observed. Data were statistically analysed with Wilcoxon rank sum test and Bonferroni correction. Results: (1) Each prepared cell sheet had a diameter of about 8 cm and was about 49 cm(2) in size, containing 2 or 3 layers of keratinocytes and fibroblasts. (2) A total of 43 patients were enrolled, of whom 3 patients dropped out of the study. Of the 40 patients who completed the treatment, there were 22 males and 18 females who were aged 1 to 57 year (s), with total burn area of 2% to 26% TBSA. (3) On treatment day 5, 7, 10, and 14, the wound healing rates in cell sheet group were significantly higher than those in conventional treatment group (Z=4.205, 4.258, 3.495, 2.521, P<0.05 or P<0.01). The complete wound healing time in cell sheet group was 7 (6, 8) days, which was significantly shorter than 11 (7, 14) days in conventional treatment group (Z=4.219, P<0.01). The total number of wound dressing changes in cell sheet group was 1 (1, 2) times, which was significantly less than 6 (4, 7) times in conventional treatment group (Z=5.464, P<0.01). (4) The wounds in cell sheet group in 31 patients healed before the first dressing change. The pain score of wounds in the first dressing change in cell sheet group of 9 patients was 1 (0, 1) point, while the pain score of wounds in the first dressing change in conventional treatment group of 40 patients was 2 (1, 3) points. There was no obvious infection in the wounds in both groups of 40 patients before the wound healing. Nine patients completed the follow-up after the trial. In 6 patients, no scar formation was observed in cell sheet group or conventional treatment group. The color of wounds in cell sheet group was consistent with normal skin, and there was only a small amount of pigment deposition in the wounds of conventional treatment group. Three patients developed pigment deposition only in the wounds of cell sheet group but obvious scars in conventional treatment group. (5) The abnormal fluctuations of vital signs including body temperature, blood pressure, heart rate, respiratory rate, and laboratory examination indexes of all patients during treatment were alleviated through the process of burn wound healing. No obvious adverse reactions or abnormalities related to the treatment were observed. Conclusions: The cell sheet containing allogeneic keratinocytes and fibroblasts can reduce the number of dressing changes, accelerate wound epithelialization, shorten wound healing time, reduce pain during dressing change in the treatment of partial-thickness burn wounds, and it may reduce scar hyperplasia after wound healing because of accelerating wound epithelization. Its clinical application is simple, safe, and effective.

[Immunodeficiency diseases with interstitial lung disease as major clinical manifestations: report of six cases].

Objective: To summarize the clinical features of immunodeficiency diseases with interstitial lung disease (ILD) as major clinical manifestations and to improve understanding etiology of ILD. Methods: The clinical features and clinical clues for diagnosis of six cases with immunodeficiency presented with ILD in Shenzhen Children's Hospital from January 2014 to December 2016 were retrospectively analyzed. Results: The patients' age ranged from 3 months to 5 years and 9 months, 5 cases were male. All cases had cough and tachypnea, 3 cases had lung infection and respiratory failure, 2 cases had chronic hypoxia and one had clubbing. Three cases had skin rashes; 5 cases had failure to thrive. Chest CT scan showed diffuse ground glass opacity in all the 6 cases, and 2 cases had cystic changes and one had "crazy-paving" pattern. Five patients were suspected to have surfactant dysfunction and genetic testing was performed before diagnosis of immunodeficiency, of which the results were negative. With human immunodeficiency virus antibody test or immunologic laboratory testing and/or immune genetic panel, acquired immune deficiency syndrome was confirmed in one case, hyper-IgM syndrome was confirmed in two cases and hyper-IgE syndrome in one case, Wiskott-Aldrich syndrome in one and STAT3 gain of function genetic mutation in another. All cases had clinical clues indicative of underlying immunocompromise. Conclusions: The clinical features of immunodeficiency diseases with ILD are cough, tachypnea or hypoxia, respiratory failure with infection, diffuse ground glass opacity in Chest CT imaging. With thorough medical history and immunology screening, there would be clinical clues indicative of underlying immunocompromise. Screening for immunodeficiency disease should be emphasized in the differential diagnosis of ILD, otherwise it may lead to misdiagnosis or unnecessary testing.

[Mechanism of renal injury and apoptosis in rats with nephrotic syndrome induced by mercury].

Objective: To investigate the relationship between renal injury and apoptosis in rats with nephrotic syndrome induced by mercury, in order to find out the pathogenesis. Methods: Forty-eight healthy male SPF-grade BN (Brown-Norway) rats were divided into the control group and the exposure group by random number table. The nephrotic syndrome was caused by subcutaneous injection of HgCl(2) (1 mg/ml) in the abdominal weight per kg of body weight. The control group was injected with the same volume of NaCl as the exposure group. Some rats were sacrificed on the 14th, 21st, 28th, and 35th days, and the serum kidney injury indicators creatinine (CRE) and urea nitrogen (BUN) were detected, and the renal tissue mercury content was detected; the in situ terminal transferase labeling technology (TUNEL) was detected Apoptosis, immunofluorescence detection of Cyt C content, Western blot detection of mitochondrial pathway apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2) , Bcl-2 related X protein (BAX) , cysteine proteinase 3 (Caspase 3) ], mitogen-activated protein kinase (MAPK) signaling pathway-related proteins[p38 mitogen-activated protein kinase (P38MAPK) , extracellular regulatory protein kinase (ERK) ] expression. Results: Compared with the control group, the BUN content in the serum of rats in the exposure group was significantly increased on days 7, 21, and 28, the CRE content was significantly increased on 21 days, the CRE content was significantly decreased on 28 and 35 days, and the organ coefficient and renal mercury content were 14 to 35 days. Significantly increased, and the differences were statistically significant (P<0.05) . Compared with the control group, rats in the exposed group showed increased glomerular stroma, tubule dilatation and other renal cell apoptosis at 14 to 35 days, and Cyt C expression was obvious in the exposed groups at 14, 21 days. Compared with the control group, the BAX content of the rats in the exposed group was significantly increased on the 21st day, the content of Caspase 3 in the rats on the 14th and 21st days was significantly increased, and the content of the P38MAPK in the 35th day was significantly increased (P<0.05) . Conclusion: HgCl(2) may cause renal cell damage through the mitochondrial pathway of apoptosis and cause nephrotic syndrome, and the MAPK signaling pathway may regulate this process and exert an inhibitory effect on apoptosis.

[Genetic variants in the surfactant protein C gene 218 site are associated with pediatric interstitial lung disease: seven cases study].

Objective: To investigate the clinical features and outcomes of pulmonary surfactant protein C gene (SFTPC) 218 site mutation in children with pulmonary interstitial disease. Methods: In this retrospective study, the clinical data, outcomes and influencing factors of 7 cases of SFTPC gene 218 site mutations in infants with interstitial lung disease in three hospitals from January 2013 to December 2016 were analyzed. Results: Seven cases were full-term children, 4 cases had the onset within 3 months after birth, 2 cases after 1 year old, 1 case within 3 months to 1 year, clinical manifestations of these cases were cough, shortness of breath, dyspnea, and limited growth and development, could not maintain life without additional oxygen supplementation, blood gas analysis showed hypoxemia, 4 cases had clubbing. Chest CT showed diffuse ground glass-like change in both lungs. Three cases were positive for cytomegalovirus (CMV)-IgM or CMV-DNA. The mutations in 7 cases were exon 3, 5 of which were SFTPC gene c.218T>C, p.lle73Thr (heterozygous mutation), and 2 cases were SFTPC gene c.218T>A, p.lle73Asn (homozygous mutation), 1 case combined with ABCA3 gene mutations. Four patients were treated with prednisone alone, one with prednisone plus hydroxychloroquine, and two with symptomatic treatment. Three patients died, 3 patients improved, and 1 patient was lost to follow-up. Conclusions: The severity and prognosis of the children with SP-C 218 site mutation may be affected by many factors. Some children who received glucocorticoid alone do not have a good response.

[The role of SWE and ATA(2015) guidelines combined mode in differentiation malignant from benign of Bethesda â ¢ thyroid nodules].

Objective: To evaluate the diagnostic value of the ATA (2015) ultrasound model, shear wave elastography (SWE), and ATA (2015)+SWE combinative modality for the diagnostic efficiency in thyroid nodules with Bethesda Classification Ⅲ indeterminate cytology, determine the diagnostic value of ultrasonography in Bethesda Classification Ⅲ indeterminate cytology.Method:216 thyroid nodules that were initially diagnosed as AUS/FLUS by fine needle aspiration (FNA) were included in this study. The clinical data and two-dimensional ultrasonographic features were compared between the benign and malignant nodules. The two-dimensional ultrasound images of all nodules were sorted by the 2015ATA guideline ultrasound model grading criteria. The maximum and average shear wave velocity (SWV) values were obtained from multiple SWV measurement under the VTIQ speed mode. The optimal threshold drawing from ROC curve and diagnostic performance of single and combinative modality were calculated.Result:①There was no significant difference in age, sex and nodule size between benign and malignant nodules (P>0.05). Malignant nodules of 152 cases of AUS thyroid nodules had significantly higher rates of not well-circumscribed margin and presence of microcalcifications (P=0.005,P=0.004). ②There were significant differences in malignancy risk among the different US patterns defined by the 2015 ATA guidelines in AUS nodules. ③The maximum and mean SWV of AUS/FLUS nodules measured in VTIQ mode were statistically significant in evaluating benign and malignant nodules. ④The area under ROC curves of ATA (2015)+SWE combined mode was 0.912, larger than single diagnosis mode ［ATA (2015):0.854, SWE: 0.862］.Conclusion:SWE can not only compensate for the deficiency of ATA (2015) in the diagnosis of benign and malignant FLUS thyroid nodules, but also effectively improve the diagnostic performance of ATA (2015) in the differentiation of benign and malignant AUS thyroid nodules.

[Clinical significance and correlation of ductular reaction in hepatobiliary diseases].

Ductular reaction is a kind of repair response to biliary and hepatocellular injury, and the pathological changes include lobular bile duct hyperplasia, matrix change and inflammatory cell infiltrations. In human liver, a ductular reaction originates from the activation and proliferation of hepatic progenitor cells. The activated hepatic progenitor cells, the intermediate hepatocytes and the reactive small bile duct cells together form the cell complex of ductular reaction, which has the dual characteristics of hepatobiliary system and co-expresses the hepatocyte and cholangiocyte antigen. Ductular reaction appears in all kinds of acute and chronic hepatobiliary injury, and plays an important role in liver regeneration and repair, fibrogenesis, cirrhosis formation, and hepatobiliary cancer occurrence and development. Understanding the pathological features and pathophysiological mechanisms of ductular reaction in various clinical hepatobiliary diseases and their role in liver regeneration can provide important suggestion for further exploring new-targeted treatment approach.

[Exposure-preceding-outcome regarding time sequence among cohort studies in real world].

One of the commonly accepted merits of cohort studies (CSs) refers to the exposure precedes outcome superior to other observational designs. We use Directed Acyclic Graphs to construct a causal graph among research populations under CSs. We notice that the substitution of research population in place of a susceptible one can be used for effect estimation. Its correctness depends on the outcome-free status of the substituted population and the performance of both screening and diagnosis regarding the outcomes under study at baseline. The temporal precedence of exposure over outcome occurs theoretically, despite the opposite happens in realities. Correct effect estimate is affected by both the suitability of population substitution and the validities of outcome identification and exclusion.

[A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease].

Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed). Result: The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography (HRCT) revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation (c.1755delC+c.2890G>A) in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion: c.1755delC+c.2890G>A is a new kind of compound heterozygous mutation in ABCA3, which can cause children's diffuse parenchymal lung disease. Its phenotype is related to its genotype.

[Clinical manifestations of three cases of surfactant protein C p. V39L mutation].

Objective: To investigate the clinical manifestations of surfactant protein C gene (SFTPC) exon-2 c. 115G>G/T (p.V39L). Method: Patients were screened for the entire coding sequence of SFTPC. Three cases from three children's hospital with mutation in p. V39L were reported. Result: All the three cases were females. The age of onset ranged from 2 months to 7 years. Two cases had recurrent lower respiratory tract infection and failed to thrive. One had chronic anoxia and clubbing fingers. Chest computed tomography (CT) showed diffused ground glass pattern, localized emphysema and intralobular septal thickening. In one case, early sign of cyst formation was also shown on CT. Two were lost to follow-up after alleviation of acute respiratory infection. One was treated with oral low-dose azithromycin and nebulized budesonide and terbutaline. She had recurrent lower respiratory tract infection in more than one year of follow-up. Conclusion: Mutations in SFTPC p. V39L cause interstitial lung diseases. Clinical manifestations included recurrent respiratory tract infections, chronic lung disease. Chest CT showing diffused ground glass pattern, localized emphysema, intralobular septal thickening and early sign of cyst formation. The treatment and prognosis need further study.

[Factors influencing antiretroviral therapy adherence among HIV-infected people on antiretroviral therapy in Ili Kazakh Autonomous Prefecture].

Objective: To analyze factors influencing antiretroviral therapy (ART) adherence among human immunodeficiency virus (HIV) patients receiving ART at the town level in Ili Kazakh Autonomous Prefecture (Ili) in May 2015 and to document enhanced ART for acquired immunodeficiency syndrome (AIDS) cases. Methods: A cross-sectional survey was conducted using one-on-one interviews and data collection from the system of AIDS follow-up management in three ART services centers at the town level of Ili. The subjects were HIV-infected individuals, aged 18 years or older, who were receiving ART during the survey. The surveys collected demographic characteristics, information related to ART and status of engaging ART, smoking and drinking behavior, depression, and quality of life. Results: A total of 412 participants completed the survey. The age was (41.1±8.0) years (range, 19-67 years). Approximately 60.9% (251) were male and 39.1% (161) were female. The survey showed that 75.0% (309) of participants were in good adherence and the P(50) (P(25), P(75)) of quality of life was 56.31 (50.55, 59.42). Females demonstrated better adherence to ART (82.6% (n=133)) than males (70.1% (n=76)) (χ(2)=8.16, P=0.005). The compliance rate of participants (78.0% (n=54)) with depression was higher than non-depressed participants (63.5% (n=255)) (χ(2)=7.52, P=0.008). Multivariate logistic regression analyses showed that the probability of good adherence to ART increased with increasing quality of life (OR=1.06, 95%CI:1.02-1.09). Moreover, participants who consumed alcohol or disclosed their HIV infection status to families were less likely to have good adherence to ART (OR=0.26, 95% CI:0.13-0.53 and OR=0.31, 95% CI:0.13-0.72, respectively). Additionally, employed participants were also less likely to have good adherence to ART compared with unemployed participants (OR=0.45, 95% CI:0.21-0.97). Conclusion: HIV/AIDS patients primarily showed good adherence to ART. Factors related to ART adherence included alcohol consumption, informing family of infection, work status, and quality of life.

Regulatory T-cell depletion in the gut caused by integrin ß7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity.

Integrin α4ß7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4ß7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin ß7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated ß7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in ß7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4ß7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.