Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to traditional SC delivery systems are therefore needed to support higher-volume biologic formulations and to reduce development time and other risks associated with high-concentration biologic formulations. Here, we outline key considerations for SC biologic drug formulations and delivery and explore a paradigm shift: the flexibility afforded by low-to-moderate-concentration drugs in high-volume formulations as an alternative to the traditionally difficult approach of high-concentration, low-volume SC formulation delivery.

Whole-genome sequencing analysis in fetal structural anomalies: novel phenotype-genotype discoveries.

OBJECTIVES: The identification of structural variants and single-nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole-genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. METHODS: We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ-T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). RESULTS: Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon-level copy-number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. CONCLUSIONS: Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, where routine genetic tests have failed to diagnose. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[Treatment and prognosis analysis of 488 patients with FIGO 2018 stage â ¢c squamous cervical cancer].

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

[Research progress on the disease burden of pneumoconiosis in China].

Pneumoconiosis is the largest and most serious disease among the legal occupational diseases in China, which causes long-term heavy disease burden to individuals, enterprises and society. How to scientifically and reasonably measure and reduce the health impact and economic loss caused by pneumoconiosis has become a key and difficult research topic. In recent years, with the development of global burden of disease (GBD) research, some scholars have adopted disease burden index to evaluate the disease burden of pneumoconiosis, but the research results and data are relatively independent, and there is a lack of systematic evaluation system and framework. This paper summarized the application of disease burden assessment index for pneumoconiosis, epidemiological and economic burden of pneumoconiosis, and the cost-effectiveness of reducing the burden. This paper aims to understand the present situation of pneumoconiosis disease burden in our country, discover the problems and challenges of pneumoconiosis disease burden research in our country now. It provides scientific basis for the research and application of pneumoconiosis and other occupational disease burden in China, as well as the formulation of comprehensive intervention measures, optimization of health resources allocation and reduction of disease burden.

[Analysis on disease burden and trend of occupational lung disease in Tianjin from 2010 to 2019 based on disability adjusted life years].

Objective: To analyze the level and trend of occupational pneumoconiosis disease burden in Tianjin from 2010 to 2019, and to provide scientific basis for making prevention and control countermeasures and suggestions. Methods: In June 2021, the data of occupational pneumoconiosis cases in Tianjin from 2010 to 2019 were selected from Follow-up survey of occupational pneumoconiosis patients in Tianjin and occupational "Health Hazardous Surveillance Information System", the subsystem of China Disease Control and Prevention Information System. Disability-adjusted life year (DALY) , years of life lost (YLL) and years lost due to disability (YLD) were used to comprehensively measure the disease burden of occupational pneumoconiosis by region, year, disease type, industry, sex and age; Kruskal-wallis H test was used for univariate analysis of DALY loss in pneumdo-niosis occupational. Results: A total of 43089 person-years of DALY due to pneumoconiosis in Tianjin from 2010 to 2019, of which the YLD accounted for about 2/3 (28277 person-years) , the YLL accounted for about 1/3 (14812 person-years) , and the average DALY was 7.34 person-years. The industrial distribution of pneumoconiosis burden in Tianjin was mainly concentrated in the manufacturing industry accounting for 90.6% of the whole industry. The disease types were mainly concentrated in silicosis, foundry pneumoconiosis, asbestosis and cement pneumoconiosis accounting for 34.4%, 16.9%, 13.3% and 10.5%, and the age distribution was mainly concentrated in the 50~<85 years old age group, accouling for 83.6%. The median DALY of occupational pneumoconiosis patients with different pneumoconiosis stages, disability grades and years of service exposed to dust were statistically significant (P<0.05) . Conclusion: The disease burden of occupational pneumoconiosis in Tianjin was still serious. It is necessary to take targeted intervention measures for key industries and population.

[Effect of miR-204 targeted regulation of DVL3 gene in silica-induced mouse lung epithelial cells].

Objective: To construct a recombinant lentiviral vector for mouse miR-204 overexpression, and to verify the targeted regulation of miR-204 and DVL3 in silica (SiO(2)) -induced mouse lung epithelial cells (MLE-12 cells) . Methods: In October 2019, the pre-miR-204 gene was amplified from the mouse genome by the polymerase chain reaction (PCR) method. After sequencing, the amplified product was cloned into the pLenti-CMV-EGFP lentiviral vector. The positive clones were identified by PCR screening and sequencing. The miR-204 overexpressed lentiviral vector was transfected into 293T cells, and lentiviral packaging and titer determination were performed. The experiment was divided into SiO(2) control group, virus control group, and miR-204 virus group, and the expressions of miR-204 and DVL3 gene were detected by real-time PCR. Results: The miR-204 lentiviral expression vector Lv-miR-204-5p was constructed and identified correctly by PCR and sequencing, and a virus dilution with a titer of 9.57×10(8) IU/ml was obtained. The results of real-time PCR showed that the expression of miR-204 in MLE-12 cells of the miR-204 virus group was higher than that of SiO(2) control group and virus control group, and the expression of DVL3 gene was lower than that of SiO(2) control group and virus control group, the differences were statistically significant (P<0.05) . Conclusion: Overexpression of miR-204 by lentiviral vector may inhibit the expression of DVL3 gene in silica-induced mouse lung epithelial cells.

[Predictive value of D-dimer for deep venous thrombosis of lower extremity in adult burn patients].

Objective: To investigate the predictive value of D-dimer for deep venous thrombosis (DVT) of lower extremity in adult burn patients. Methods: A retrospective case series study was conducted. The clinical data of 3 861 adult burn patients who met the inclusion criteria and were admitted to the Department of Burns of Zhengzhou First People's Hospital from January 1, 2015 to December 31, 2019 were collected. The patients were divided into DVT group (n=77) and non-DVT group (n=3 784) according to whether DVT of lower extremity occurred during hospitalization or not. Data of patients in the two groups were collected and compared, including the gender, age, total burn area, D-dimer level, with lower limb burn and inhalation injury or not on admission, with sepsis/septic shock, femoral vein indwelling central venous catheter (CVC), history of surgery, and infusion of concentrated red blood cells or not during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors for DVT of lower extremity in 3 861 adult burn patients. The receiver operating characteristic (ROC) curve of the independent risk factors predicting DVT of lower extremity in 3 861 adult burn patients were drawn, and the area under the curve (AUC), the optimal threshold value, and the sensitivity and specificity under the optimal threshold value were calculated. The quality of the AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold value were compared using chi-square test. Results: There were no statistically significant differences in gender, occurrence of sepsis/septic shock or history of surgery during hospitalization between patients in the two groups (P>0.05), while there were statistically significant differences in age, total burn area, D-dimer level, lower limb burn and inhalation injury on admission, and femoral vein indwelling CVC and infusion of concentrated red blood cells during hospitalization between patients in the two groups (t=-8.17, with Z values of -5.04 and -10.83, respectively, χ2 values of 21.83, 5.37, 7.75, and 4.52, respectively, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that age, total burn area, and D-dimer level were the independent risk factors for DVT of lower extremity in 3 861 adult burn patients (with odds ratios of 1.05, 1.02, and 1.14, respectively, 95% confidence intervals of 1.04-1.06, 1.00-1.03, and 1.10-1.20, respectively, P<0.05 or P<0.01). The AUCs of ROC of age, total burn area, and D-dimer level for predicting DVT of lower extremity in 3 861 adult burn patients were 0.74, 0.67, and 0.86, respectively (with 95% confidence intervals of 0.68-0.80, 0.60-0.74, and 0.83-0.89, respectively, P values<0.01), the optimal threshold values were 50.5 years old, 10.5% total body surface area, and 1.845 mg/L, respectively, the sensitivity under the optimal threshold values were 71.4%, 70.1%, and 87.0%, respectively, and the specificity under the optimal threshold values were 66.8%, 67.2%, and 72.9%, respectively. The AUC quality and sensitivity and specificity under the optimal threshold value of D-dimer level were significantly better than those of age (z=3.29, with χ2 values of 284.91 and 34.25, respectively, P<0.01) and total burn area (z=4.98, with χ2 values of 326.79 and 29.88, respectively, P<0.01), while the AUC quality and sensitivity and specificity under the optimal threshold values were similar between age and total burn area (P>0.05). Conclusions: D-dimer level is an independent risk factor for DVT of lower extremity in adult burn patients, its AUC quality and sensitivity and specificity under the optimal threshold value are better than those of age and total burn area, and it has good predictive value for DVT of lower extremity in adult burn patients.

[Short-term efficacy of anti-IgE monoclonal antibody in patients with recurrent chronic rhinosinusitis with nasal polyps combined with asthma].

Objective: To investigate the short-term efficacy of anti-IgE monoclonal antibody (Omalizumab) in the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) complicated with asthma. Methods: Patients with recurrent CRSwNP and comorbid asthma in Beijing TongRen Hospital from May to December of 2020 were continuously recruited and received a 4-month therapy of stable background treatment plus Omalizumab. Results of visual analog scales (VAS) of nasal symptoms, sino-nasal outcome test-22 (SNOT 22) and nasal polyp scores were collected at baseline and post-treatment (1, 2, 3 and 4 months after treatment). Blood routine tests, total nasal resistances (TNR), minimum cross-sectional areas (MCA), total nasal cavity volumes (NCV), forced expiratory volumes in one second (FEV1)/forced vital capacity (FVC) and adverse events were collected at baseline and 4 months after treatment. All results were evaluated for short-term efficacy of Omalizumab. GraphPad Prism 8.2.1 was used for statistic analysis. Results: Ten patients were collected, including 3 males and 7 females, aged (41.13±12.64) years old (x¯±s). Compared to results at baseline, the VAS scores of nasal obstruction, rhinorrhea, hyposmia and headache after 4 months treatment were significantly decreased (1.80±1.48 vs 6.70±2.83, 2.40±1.27 vs 6.40±3.44, 2.70±2.91 vs 8.20±2.25, 0.60±1.08 vs 3.60±2.72, t value was 5.045, 4.243, 5.312, 3.402, respectively, all P<0.01). The scores of SNOT-22 (25.6±20 vs 61.3±33.32, t=4.127, P=0.002 6), nasal polyp scores (2.20±0.92 vs 4.60±0.84, t=9.000, P<0.01) and the count and percentage of eosinophils in peripheral blood were significantly decreased ((94.10±97.78)×109/L vs (360.00±210.80)×109/L, (32.90±27.06)% vs (64.40±20.73)%, t value was 3.678, 2.957, respectively, all P<0.05). NCV (0-5 cm and 0-7 cm) of patients were improved from baseline ((12.62±2.84) cm3 vs (10.40±2.09) cm3, (27.50±14.15) cm3 vs (16.81±6.40) cm3, t value was 2.371, 2.445, respectively, all P<0.05). Conclusions: The 4-month treatment of Omalizumab can significantly improve the nasal symptoms and quality of life of patients with recurrent CRSwNP complicated with asthma, shrink nasal polyps size and reduce the number of peripheral blood eosinophils. Omalizumab can be used as an alternative therapy for refractory CRSwNP patients in the future.

Knowledge, Attitude and Preventive Practice on Dementia Care among Primary Health Professionals in Macao.

The Macao Dementia Policy was recognized by Alzheimer Disease International as the 27th globally and one of the highest stage 5 to develop dementia friendly community and primary health professionals are in a pivotal position to enhance community-based dementia prevention and care quality. This study aimed to investigate the knowledge, attitude and preventive practice on dementia care among primary health professionals in Macao. A specially designed 30-item questionnaire was developed and validated for the study. The Content Validity Index (CVI) and Cronbach's α of the questionnaire were 0.973 and 0.808. The questionnaires were distributed to all 375 primary health professionals from 8 Health Centers throughout Macao and 234 valid questionnaires (62.4%) were returned. The score for dementia care knowledge was 87.02±14.01; attitude was 69.52±5.83; preventive practice was 77.88±13.18, of which doctors (79.89±13.77) was significantly higher (t=2.29, p=0.023) than nurses (75.91±12.33). There were positive relationships between preventive practice and attitude (r=0.163, p=0.014), and age (r=0.212, p=0.002), and a negative relationship between knowledge and age (r=-0.139, p=0.040). These findings have significant implications that most primary health professionals in Macao had sufficient knowledge, a positive attitude and appropriate preventive practice on dementia care. However, enhanced dementia education to improve knowledge and preventive practice was a strong agenda for the training for senior staff and nurses.

Effectiveness of recombinant human granulocyte macrophage colony-stimulating factor for treating deep second-degree burns: a systematic review and meta-analysis.

INTRODUCTION: It is uncertain whether treatment by recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) can promote healing of deep second-degree burns. This meta-analysis aimed to systematically review and assess randomised controlled trials (RCTs) that investigated the efficacy and safety of rhGM-CSF for treating deep second-degree burns. METHODS: This meta-analysis conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The PubMed, Cochrane Library, Medline and Embase databases and relevant references were systematically searched for RCTs (published up to November 2019). Main outcome measures included the wound healing rate, wound healing time and average optical densities of the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). We performed a meta-analysis using fixed or random effects models. RESULTS: Seven RCTs comprising 982 patients with 1184 burns (652 patients received rhGM-CSF vs 532 controls) were included. Compared with standard wound care alone, the use of rhGM-CSF significantly reduced wound healing time by 4.77 days (weighted mean difference=-4.77; 95% CI -6.45 to -3.09; p<0.001) and significantly increased the wound healing rate on days 7, 10, 14 and 20 by 6.46%, 19.78%, 17.07% and 11.38%, respectively. There was no significant difference between the groups in the wound healing rate on day 28 and average optical densities of VEGF and FGF. No systematic adverse event occurred. Redder, more swollen and painful wounds were reported after using rhGM-CSF compared with the control. CONCLUSIONS: rhGM-CSF could be effective and safe for treating deep second-degree burns.

Long-term outcomes of different endoscopic sinus surgery in recurrent chronic rhinosinusitis with nasal polyps and asthma.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma have poorer outcomes after functional endoscopic sinus surgery (FESS) and higher recurrence rate. The aim of present study was to investigate the long-term clinical outcomes of extended surgical strategies for patients with recurrent CRSwNP and asthma. METHODS: Eighty-one patients with CRSwNP and asthma were enrolled in this 5-year prospective study. They were randomly assigned to undergo FESS, radical endoscopic sinus surgery (RESS), or RESS+Draf 3 surgery. Disease severity and clinical outcomes were evaluated using symptoms scoring, endoscopic scoring system, computed tomography staging system, sinus-specific quality of life scores, tissue and peripheral blood eosinophil percentage, and pulmonary function tests. Baseline, 1-year, 3-year, and 5-year follow-up data were compared among the groups. RESULTS: RESS and RESS+Draf 3 strategies yielded better short-term (1 year) outcomes than did FESS. FESS had a higher short-term recurrence rate, although recurrence rates were similarly high (95.6 - 96.1%) in all the groups at 5 years postoperatively. RESS and RESS+Draf 3 yielded a lower long-term revision surgery rate and a longer time to recurrence post-surgery than FESS, which was negatively correlated with tissue and peripheral blood eosinophil percentage. CONCLUSIONS: CRSwNP with asthma is a systemic disease that inevitably recurs. Radical surgery prolongs recurrence time and improves olfaction, rhinorrhea, and quality of life in the short-term. Combining Draf 3 with RESS did not yield better clinical outcomes than RESS alone; thus, although RESS alone appears to be the best option, these findings need to be confirmed in further studies involving more patients, longer follow-up duration and stricter standardized medication use especially the adequate steroid irrigations.

Pathological changes from the originating to the peripheral sites of Sinonasal Inverted Papilloma are the underlying mechanisms of preoperative MRI-tumor origin prediction.

BACKGROUND: Our previous study showed that convoluted cerebriform pattern (CCP)-based reverse tracing method in preoperative magnetic resonance imaging (MRI) is a reliable tool in predicting originating site of sinonasal inverted papilloma (SNIP). This study aimed to determine the underlying pathological mechanism of the preoperative MRI-CCP reverse tracing method by assessing the histopathological changes from the origin to the peripheral sites of SNIP. METHODOLOGY: The originating site of SNIP was predicted by preoperative MRI in 30 consecutive patients suspected to have primary SNIP. Samples of SNIP originating and peripheral sites were processed by pathological staining for evaluation of stroma score, micro-vessel density (MVD), and tight junction proteins (claudin-5, zonula occludens (ZO)-1 and occludin) expression. RESULTS: The originating site of SNIP was accurately predicted by preoperative MRI in all patients. Stroma scores, and MVD were significantly greater in the periphery of SNIP than in the originating site. In contrast, Claudin-5 expression in micro-vessels was greater at the originating site than the periphery. CONCLUSIONS: More edematous stroma and intensive micro-vessels with defective tight junction in periphery of SNIP result in more contrast agent diffusing and CCP that can only be observed at the periphery of SNIP on T2 and contrast-enhanced T1 weighted MR images, which may be the mechanisms underlying the CCP reverse tracing method.

[Clinical characteristics and drug susceptibility test of nontuberculous mycobacterial lung disease].

Objective: To investigate the clinical characteristics and drug susceptibility test (DST) of patients infected with different nontuberculous mycobacteria (NTM). Methods: The patients with nontuberculous mycobacterial lung disease (NMLD) in Shanghai Pulmonary Hospital from March 2014 to March 2015 were studied retrospectively by analyzing the clinical characteristics, radiological features and DST results. A total of 201 NMLD patients [male 108, age(58±15) yrs] were enrolled into this study including 48 cases of M. Kansasii [male 13, age (52±16) yrs],46 cases of M. Abscess[male 46, age (57±16) yrs], 92 cases of M. Intracellulare [male 43, age (61±13) yrs], and 15 cases of M. Avium [male 6, age (67±10) yrs]. Clinical data were collected when the diagnosis was made and Chi-square test was used to compare the differences among 4 groups of patients. Bonferroni method was used for further pairwise comparisons. Results: There were significant differences among the 4 groups in the age(χ(2)=6.42, P<0.001) and the gender(χ(2)=49.18, P<0.001) of the patients. The history of bronchiectasis in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 2/48, 31/46, 39/92 and 4/15 cases respectively(χ(2)=41.84, P<0.001). For the Gamma-interferon release assays (ELISA) (IGRA), the positive rate of IGRA in the groups of M. Kansasii, M. Abscess, M. Intracellulare and M. Avium were 83%(40/48), 30%(14/46), 23%(21/92) and 33% (5/15) respectively(χ(2)=50.96, P<0.001). The radiological features were significantly different in tree-in-bud(8/48, 35/46, 36/92 and 4/15 cases respectively, χ(2)=36.48, P<0.001), pleural thickness or mild effusion (21/48, 36/46, 69/92 and 7/15 cases, χ(2)=19.54, P<0.001), bronchiectasis (20/48, 39/46, 78/92 and 10/15 cases, P<0.001) and cavities (38/48, 21/46, 63/92 and 10/15 cases, χ(2)=12.38, P<0.001) among the 4 groups(M. Kansasii, M. Abscess, M. Intracellulare and M. Avium). The drug resistance rates of M. Kansasii to rifampin, ethambutanol and ofloxacin were 10%(5/48), 8%(4/48) and 15%(7/48) respectively; the resistance rates of M.Intracellulare to ethambutanol was 45%(41/92), and the resistance rates of M.Abscess were all over 80% to all anti-TB drugs. The results of pairwise comparisons showed that the male proportion(46/48) and IGRAs positive rate(40/48) of patients with M. Kansasii were higher than those of other groups, and the incidence of bronchiectasis(20/48) and pleural changes(21/48) was lower than those of other groups. The female ratio(33/46), history of bronchiectasis (31/46) and tree-in-bud sign of patients(35/46) with M. Abscess were higher than those of other groups. Conclusions: There were differences in the clinical manifestations and imaging features of 4 common NMLD diseases, which were helpful for clinical differentiation. The patients with M. Kansasii infection were mainly male, with a high IGRA positive rate and fewer lesions of bronchiectasis or pleural changes. Most of the patients with M. Abscess were female, with a previous history of bronchiectasis, and with most of the lesions showing tree-in-bud signs. The NTM species had a high rate of resistance to anti-TB drugs except M. Kansasii.

Role of miR-21 in rats with proliferative diabetic retinopathy via TGF-ß signaling pathway.

OBJECTIVE: To explore the effects of miR-21 on the rats with proliferative diabetic retinopathy by regulating the transforming growth factor-beta (TGF-ß) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into the normal group (n=12), model group (n=12), and inhibitor group (TGF-ß signaling inhibitor) (n=12). No treatment was performed in the normal group, the diabetic retinopathy model was established in the model group, and the model was established in the inhibitor group after the intraperitoneal injection of the inhibitor. Then, the materials were sampled for detection. In each group, the retinal morphology was observed via hematoxylin-eosin (HE) staining, the expressions of TGF-ß1 and Smad3 were detected via immunohistochemistry, the relative protein expression levels of phosphorylated Smad3 (p-Smad3) and TGF-ß were determined via Western blotting, the expression of miR-21 was detected via quantitative Polymerase Chain Reaction (qPCR), and the hemodynamic indicators of the ocular tissues were detected using the color Doppler ultrasonography. RESULTS: The HE staining results revealed that the rats in the model group had evident retinal damage, which could be effectively improved using the inhibitor. According to the immunohistochemistry detection results, the positive expression level of TGF-ß1 was substantially raised in both model group and inhibitor group compared with that in the normal group (p<0.05), and it was notably lower in the inhibitor group than that in the model group (p<0.05). Moreover, the three groups did not differ in the positive expression level of Smad3 (p>0.05). The Western blotting results showed that the model and inhibitor groups had remarkably higher relative protein expression levels of p-Smad3 and TGF-ß1 than the normal group (p<0.05), and they were markedly lowered in the inhibitor group compared with those in the model group (p<0.05). According to the qPCR results, the expression level of miR-21 was notably elevated in both model group and inhibitor group compared with that in the normal group (p<0.05), and there was no difference in the expression level of miR-21 between the former two groups (p>0.05). Finally, based on the color Doppler ultrasonography findings, the levels of the hemodynamic indicators substantially declined in both model group and inhibitor group compared with those in the normal group (p<0.05), and they were notably higher in the inhibitor group than those in the model group. CONCLUSIONS: We found that miR-21 regulates the TGF-ß signaling pathway to affect the hemodynamics in the rats with proliferative diabetic retinopathy.

[Clinical significance of serum squamous cell carcinoma antigen in patients with early cervical squamous cell carcinoma].

Objective: To explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) in early cervical squamous cell carcinoma. Methods: The clinicopathological data and follow-up information of 1435 patients with stage ⅠA2-ⅡA cervical squamous cell carcinoma were collected. The correlation between serum SCC-Ag level and clinicopathological feature and prognosis were analyzed. The best cut-off of serum SCC-Ag for predicting pelvic lymph node metastasis and survival of cervical squamous cell carcinoma patients were also identified. Results: The result of univariate analysis showed that The International Federation of Gynecology and Obstetrics (FIGO) staging, tumor size, depth of cervical stromal invasion, lymphovascular space involvement, pelvic lymph node metastasis, common iliac lymph node metastasis and para-aortic lymph node metastasis were significantly related with serum SCC-Ag level (all P<0.05). The result of multivariate logistic regression analysis showed that tumor size, depth of cervical stromal invasion, pelvic lymph node metastasis and common iliac lymph node metastasis were the independent risk factors of preoperative serum SCC-Ag>2.65 ng/ml (all P<0.001). Multivariate Cox regression analysis showed that lymphovascular space involvement, SCC-Ag>3.15 ng/ml, common iliac lymph node metastasis and tumor size >4 cm were the independent prognostic risk factors (all P<0.05). The univariate analysis showed that, the tumor size, FIGO stage, depth of cervical stromal invasion and SCC-Ag level were significantly related with the recurrence of 1 096 patients without postoperative high risk factors (all P<0.05). Multivariate logistic regression analysis showed that FIGO stage (OR=1.671) and SCC-Ag>2.65 ng/ml (OR=4.490) were the independent risk factors for recurrence (both P<0.05). The best cut off of SCC-Ag for predicting early postoperative cervical lymph node metastasis of cervical squamous cell carcinoma was 2.65 ng/ml, the sensitivity was 60.8%, the specificity was 71.8%. The best cut off of SCC-Ag for predicting prognosis of cervical squamous cell carcinoma was 3.15 ng/ml, the sensitivity was 53.5%, the specificity was 71.1%. Conclusions: Preoperative serum squamous cell carcinoma antigen is an independent prognostic risk factor of survival of patients with early cervical squamous cell carcinoma, and is significantly related with recurrence of patients without postoperative high-risk factors. It can be used as a reference factor for postoperative adjuvant radiotherapy.