[Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage â £ squamous cell carcinoma of penis].

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Effects of metabolic abnormalities, hyperandrogenemia and clomiphene on liver function parameters among Chinese women with polycystic ovary syndrome: results from a randomized controlled trial.

PURPOSE: To investigate the effects of metabolic abnormalities, hyperandrogenemia and ovulation induction by clomiphene/acupuncture on liver function parameters among women with polycystic ovary syndrome (PCOS). METHODS: This is a secondary analysis of a randomized controlled trial. All 1000 subjects were diagnosed as PCOS by modified Rotterdam criteria. Liver function parameters, metabolic panel and hormone profile were measured at baseline and after treatment. The relationship between liver parameters with metabolic, hormonal parameters and ovulation induction was examined. RESULTS: PCOS women with metabolic syndrome had higher liver enzyme levels but lower bilirubin and bile acid levels than without. PCOS women with hyperandrogenemia had higher liver enzyme, bilirubin levels than without. Correlation analyses showed that worsening of metabolic parameters was associated with higher liver enzyme levels but lower bilirubin and bile acid levels, while increased androgen levels were associated with higher liver enzyme, bilirubin and bile acid levels. Ovulation induction with clomiphene citrate could decrease bilirubin and bile acid levels, while acupuncture had no obvious effect on liver function. CONCLUSIONS: Among PCOS women, metabolic abnormalities and hyperandrogenemia impaired different liver function parameters. Clomiphene could decrease the bilirubin and bile acid levels while acupuncture had no obvious effect on liver function.

[Dosimetric comparison of the helical tomotherapy, intensity-modulated radiotherapy and volumetric-modulated arc therapy in radical radiotherapy for esophageal cancer].

Objective: To compare the dosimetric parameters of three different modern radiation techniques in radical radiotherapy for esophageal cancer. Methods: A total of 25 patients with pathologically confirmed esophageal squamous cell carcinoma in Zhejiang Cancer Hospital were included from September 2015 to May 2016 and three radiation treatment plans for helical tomotherapy (TOMO), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) were designed respectively for each patient. Study patients included 24 males and 1 female,aged from 47 to 82 years old, with a median age of 63 years old. All patients received the total prescription dose of 60 Gy in 30 fractions to the planning target volume (PTV). Conformity index (CI), heterogeneity index (HI), D(1), D(2), D(50), D(95), D(98), D(9)9 and V(95), V(100), V(105) of PTV was calculated. The mean dose, V(5), V(10), V(20), V(30), V(40) and V(50) of total lung, heart, and maximum dose (D(max)) to spinal cord were recorded as well. Results: Compared with TOMO and IMRT, VMAT showed higher CI (0.81±0.08) and lower HI (0.10±0.05), and CI was worse in IMRT (0.77±0.05) than TOMO (0.79±0.04) (t=2.604, P=0.016) and VMAT (t=2.817, P=0.010). There was no significant difference in HI among three radiation techniques. The dosimetric parameters of TOMO in normal lung were significantly better than those of VMAT and IMRT, especially in V(20) and V(30). The D(max) of spinal cord (38.24±3.72) Gy in TOMO was significantly lower than that of the VMAT ((39.88±3.27)Gy, t=-3.173, P=0.004) and IMRT plan ((41.09±3.18)Gy, t=-5.559, P=0.000). Subgroup analysis showed that VMAT was superior to TOMO and IMRT in CI and HI, especially HI (0.09±0.01) significantly better than TOMO (0.12±0.03, t=3.024, P=0.029) and IMRT (0.12±0.02, t=-3.800, P=0.013) for patients with cervical and upper thoracic esophageal cancer. TOMO and VMAT were significantly better than IMRT in MLD, lung V(20) and V(30) (all P<0.05). TOMO (38.46±2.15)Gy was significantly superior to VMAT ((41.02±1.28)Gy,t=-2.701, P=0.043) and IMRT ((41.76±1.11)Gy, t=-3.111, P=0.027) at D(max) of the spinal cord. For the patients with middle and lower thoracic esophageal cancer, TOMO, VMAT and IMRT had no statistically significant differences in CI and HI. IMRT was inferior to TOMO and VMAT in MLD, lung V(10), V(20), and V(30) (all P<0.05). TOMO (38.17±4.14) Gy was significantly superior to VMAT ((39.52±3.64)Gy,t=-2.219, P=0.040) and IMRT ((40.87±3.59)Gy,t=-4.528, P=0.000) at D(max) of the spinal cord. Conclusions: The VMAT plan is better than TOMO and IMRT in terms of the conformal degree and dose uniformity of the target volume.TOMO seems significantly better than VMAT and IMRT in protecting normal tissue.

[Effect of leader-member exchange on nurses'sense of calling in workplace].

Objective: To investigate the effect of leader-member exchange on nurses'sense of calling in workplace based on self-determination theory. Methods: A total of 381 nurses were randomly selected from five tertiary general hospitals in Zhejiang province, China from October to December, 2016. They were subjected to a survey using the Leader-Member Exchange Scale, Job Autonomy Scale, Core Self-Evaluation Scale, and Calling Scale. The mediating effect was used to test the procedures and the data were subjected to hierarchical regression analysis. Results: The leader-member exchange was positively correlated with job autonomy, core self-evaluation, and sense of calling (r=0.471, P<0.001; r=0.373, P<0.001; r=0.475, P<0.001) ; the leader-member exchange had a positive predictive effect on job autonomy and sense of calling (ß= 0.47, P<0.001; ß=0.48, P<0.001) ; the job autonomy had a partial mediating effect on the relationship between leader-member exchange and sense of calling (F=66.50, P<0.001) ; the core self-evaluation negatively adjusted the positive relationship between leader-member exchange and job autonomy (F=27.81, P<0.001) . Conclusion: High-quality leader-member exchange enhances the sense of calling by improving staffs' job autonomy and the core self-evaluation reduces the positive relationship between leader-member exchange and job autonomy.

MiR-30a suppresses non-small cell lung cancer progression through AKT signaling pathway by targeting IGF1R.

MicroRNAs play critical roles in the development and progression of human cancers. Although miR—30a has been suggested to function as a tumor repressor in several tumors, its role in non—small cell lung cancer (NSCLC) has not been investigated in detail. This study investigated the expression and role of miR—30a in human NSCLC. The expression of miR—30a is significantly decreased in clinical NSCLC tissues and cell lines. Overexpression of miR—30a inhibited NSCLC cell proliferation, G1/S and S/G2 transition in vitro, whereas suppression of miR—30a facilitated NSCLC cell proliferation, G1/S and S/G2 transition. Using a luciferase reporter assay, insulin—like growth factor 1 receptor (IGF1R) was determined to be a direct target of miR—30a. Furthermore, silencing IGF1R resulted in the same biologic effects of miR—30a overexpression in NSCLC cells, which included suppressed NSCLC cell proliferation and trigering cell cycle arrest through PI3K/AKT signaling pathway by inhibiting cell cycle regulators (CDK2, CDK4, Cyclin A2 , Cyclin D1). These results demonstrate that miR—30a influences NSCLC progression through PI3K/AKT signaling pathway by targeting IGF1R in A549 cells, which suggest miR—30a as a novel strategy for NSCLC diagnosis and treatment.

miR-106a* inhibits the proliferation of esophageal carcinoma cells by targeting CDK2-associated Cullin 1 (CACUL1).

Previous studies suggest that aberrant microRNA expression is common in plenty of cancers. The expression of miR-106a* was decreased in follicular lymphoma, but the expression and functions of miR-106a* in esophageal carcinoma (EC) remain unclear. In this study, we explored the expression and anti-oncogenic roles of miR-106a* in human EC. The expression of miR-106a* is significantly decreased in EC tissues and EC cell lines. Overexpression of miR-106a* suppressed EC cell proliferation, clonogenicity, G1/S transition, and induced apoptosis in vitro, but inhibition of miR-106a* facilitated cell proliferation, clonogenicity, G1/S transition. Luciferase reporter assay results showed that CDK2-associated Cullin 1 (CACUL1) was a direct target of miR-106a* in EC cells. Moreover, silencing CACUL1 resulted in the same biologic effects of miR-106a* overexpression in EC cells, which included suppressed EC cell proliferation, clonogenicity, and blocked G1/S transition through CDK2 pathway by inhibiting cell cycle regulators (Cyclin A, Cyclin E). Our data indicate that miR-106a* might play an anti-oncogenic role in EC by regulating CACUL1 expression, which suggest miR-106a* as a new potential diagnostic and therapeutic target for EC.

Association of the TNF-α+489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis.

The association between the TNF-α +489 G/A polymorphism and chronic obstructive pulmonary disease (COPD) remains controversial because of small group size and varied design among different studies. In the present study, a meta-analysis was conducted to assess the association between the +489 G/A polymorphism and COPD risk. A comprehensive search was conducted to identify articles that have reported an association between the TNF-α +489 G/A polymorphism and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under both dominant (AA+GA vs GG genotypes) and allele (A vs G) models. Heterogeneity was assessed, as well as publication bias. Nine articles with ten eligible studies were included in this analysis. Significant association between the +489 G/A polymorphism and COPD was identified in Asians under the allele model (OR = 1.582, 95%CI = 1.035-2.419). However, no significant difference was found in the Caucasian groups. Strong evidence for between-study heterogeneity was identified under both models, and no publication bias was detected. Our results indicated a potential role of the A allele of the TNF-α +489 G/A polymorphism in increasing COPD risk in Asians, but not in Caucasians. Additional studies will be necessary to verify this conclusion.

Association of the IGF-1 rs35767 and rs972936 polymorphisms with the risk of osteoporosis in a Chinese postmenopausal female population.

The aim of our study was to conduct a case-control study in a Chinese postmenopausal population to evaluate the roles of the IGF-1 rs35767 and rs972936 polymorphisms on bone mineral density (BMD) levels and osteoporosis risk. A total of 272 consecutive postmenopausal women with a primary diagnosis of osteoporosis and 272 controls were enrolled in the study between 2012 and 2014. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype the rs35767 and rs972936 IGF-1 polymorphisms. By comparing the demographic characteristics between patients and controls, patients with osteoporosis were found to be more likely to have a habit of alcohol drinking (P = 0.023). Furthermore, the BMD levels of the L1-L4 vertebrae, femoral necks, total hips, and trochanters in patients with osteoporosis were significantly lower than those in controls. By conditional regression analysis, we found that the IGF-1 rs2288377 and rs972936 gene polymorphisms were not associated with the risk of osteoporosis (P < 0.05). However, the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral neck. Overall, our study suggests that IGF-1 rs2288377 and rs972936 gene polymorphisms do not influence the risk osteoporosis.

Association of -238G/A and -863C/A polymorphisms in the TNF-α gene with chronic obstructive pulmonary disease based on a meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease; increasing evidence indicates that the TNF-α polymorphism is associated with progression of this disease. Few studies have focused upon association between TNF-α -238G/A or -863C/A polymorphism and COPD risk. Reported associations have been controversial because of small sample size and varied study design among the different studies. We performed a meta-analysis to assess the correlation of these two polymorphisms in the TNF-α gene with COPD risk. A comprehensive search was conducted to identify all published articles on the association between TNF-α -238G/A or -863C/A polymorphism and COPD risk from different databases. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and the heterogeneity and publication bias were assessed. Eight articles with 10 eligible studies met our inclusion criteria; six studies were of the -238G/A polymorphism and the others involved the -863C/A polymorphism. In the case of the -863C/A polymorphism, significant association was detected only in Asians in the A allele carriers (GA+AA versus GG genotype) and allele (A versus G allele) model (OR = 0.505, 95%CI = 0.321-0.795 and OR = 0.560, 95%CI = 0.368-0.851, respectively). However, no significant association was detected for the -238G/A polymorphism. No evidence of between-study heterogeneity and publication bias was detected. We suggest a potentially protective role of the A allele in the TNF-α -863C/ A polymorphism against developing COPD in Asians. This hypothesis needs further studies for confirmation.

Association of the G403A polymorphism in the RANTES gene with coronary artery disease: a meta-analysis.

The G403A polymorphism in the RANTES (regulated on activation normal T cell expressed and secreted) gene has a key role in the expression of RANTES, which has been detected in a range of cells in atherosclerotic plaque. However, the association of this polymorphism with the risk of coronary artery disease (CAD) remains controversial. A meta-analysis was performed to assess the association of the G403A polymorphism in the RANTES gene with the risk of CAD. A comprehensive search was conducted to identify all studies published on the association of the RANTES gene G403A polymorphism with CAD risk. The fixed or random-effect pooled measure was adopted based on a heterogeneity test among studies, which was evaluated using I(2). Potential sources of between-study heterogeneity were explored using meta-regression analysis. Publication bias was estimated with Begg's rank correlation method. Eight articles were included in this meta-analysis, with 4601 CAD cases and 2522 controls. No significant association of RANTES gene G403A polymorphism with CAD was identified in any of the codominant, dominant, recessive, homozygote, or heterozygote inheritance models. No evidence of publication bias was detected. The meta-analysis suggested that the A allele of the G403A polymorphism in the RANTES gene has no effect on the risk of CAD. This relationship needs to be confirmed by further studies.

[A survey of performance of public health risk assessment in emergencies of institutions for disease control and prevention at different levels in China].

Objective: To understand the performance of public health risk assessment in emergencies of institutions for disease control and prevention at different levels in China, and provide suggestions for the improvement of public health risk assessment. Methods: A self-administered survey was conducted in professionals involved in public health risk assessment in emergencies from national institution, provincial institutions and some prefectural institutions for disease control and prevention (1-2 prefectural institutions were selected using convenience sampling in each province) between March and April in 2021. Results: A total of 79 institutions for disease control and prevention were investigated, including 1 national institution, 32 provincial institutions and 46 prefectural institutions. By April 2021, all the 79 institutions surveyed had conducted risk assessment of public health emergencies, in which 61 (77.2%) had established departments responsible for the public health risk assessment, i.e. emergency management office or communicable disease prevention and control office (section), and regular risk assessment mechanisms. The main sources of information for public health risk assessment were public health surveillance systems, including the National Notifiable Diseases Reporting System (100.0%) and Public Health Emergencies Management Information System (97.5%). Compared with the provincial institutions, the prefectural institutions were more likely to use specific disease surveillance systems (84.8% vs. 62.5%; χ2=5.09, P=0.024). The risk management recommendations made by 43 institutions for disease control and prevention (54.4%) after the risk assessment were accepted by the superior health administrative departments and used in epidemic prevention and control. Conclusions: Public health risk assessment in emergencies has been widely carried out by national, provincial and prefectural institutions for disease control and prevention in China. Specialized departments and mechanisms have been established, but the information sources are still confined to public health surveillance systems and the application of the risk assessment results still needs to be further improved.

[Investigation of contamination of SARS-CoV-2 in imported frozen seafood from a foreign cargo ship and risk factors for infection in stevedores in Qingdao].

Objective: To investigate the contamination status of SARS-CoV-2 in imported frozen seafood from a Russia cargo ship in Qingdao and to analyze the risk factors for infection in local stevedores. Methods: The method of "two-stage, full coverage and mixed sampling" was used to collect the seafood packaging samples for the nucleic acid detection of SARS-CoV-2 by real-time fluorescent quantitative RT-PCR. A unified questionnaire was designed to investigate 71 stevedores in two shifts through telephone interview. The stevedores were divided into two groups, with 23 in the shit with two infections was group A and 48 in the shift without infection was group B. Software Epi Info7.2 was used to identify the risk factors for SARS-CoV-2 infections in the stevedores. Results: In the frozen seafood from a Russia cargo ship, the total positive rate of SARS-CoV-2 nucleic acid in the frozen seafood was 11.53% (106/919). The positive rate of SARS-CoV-2 nucleic acid in the frozen seafood unloaded by group A (14.29%,70/490) was significantly higher than that in the frozen seafood unloaded by group B (8.39%,36/429)(χ2=7.79,P=0.01) and the viral loads detected in the frozen seafood unloaded by group A were higher than those detected in the frozen seafood unloaded by group B. The scores of personal protection and behaviors in the stevedores in group A were significantly lower than those in group B (P<0.05), and toilet use, smoking and improper hand washing before meals were the risk factors for the infection. Conclusions: The imported frozen seafood was contaminated by SARS-CoV-2 and the contamination distribution was uneven. Supervision and management of personal occupational protection and behaviors of workers engaged in imported frozen food transportation should be strengthened. It is suggested that a closed-loop monitoring and management system for the whole process of "fishing-transport- loading/unloading" should be established by marine fishery authority.

Femtosecond laser-drilling-induced HgCdTe photodiodes.

Femtosecond-laser drilling may induce holes in HgCdTe with morphology similar to that induced by ion-milling in loophole technique. So-formed hole structures are proven to be pn junction diodes by the laser beam induced current characterization as well as the conductivity measurement. Transmission and photoluminescence spectral measurements on a n-type dominated hole-array structure give rise to different results from those of an ion-milled sample.

MiRNA-584 suppresses the progression of ovarian cancer by negatively regulating LPIN1.

OBJECTIVE: The aim of the study was to detect the expression level of microRNA-584 (miRNA-584) in ovarian cancer (OCa) and to elucidate its regulatory effect on OCa progression by regulating LPIN1. PATIENTS AND METHODS: Expression levels of miRNA-584 and LPIN1 in 31 matched OCa tissues and paracancerous tissues were detected. The relationship of miRNA-584 level with clinical indicators and prognosis of OCa patients was analyzed. Influences of miRNA-584/LPIN1 regulatory loop on malignant phenotypes of OVCAR3 and PEO1 cells were assessed. In addition, the interaction between miRNA-584 and LPIN1 was confirmed by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: MiRNA-584 was lowly expressed in OCa tissues, while LPIN1 was highly expressed. OCa patients expressing a low level of miRNA-584 suffered from higher rates of lymphatic metastasis and distant metastasis, as well as worse survival. The overexpression of miRNA-584 in OVCAR3 cells attenuated proliferative and migratory abilities, while the knockdown of miRNA-584 in PEO1 cells yielded the opposite results. LPIN1 was verified to be the target binding to miRNA-584 and its level was negatively regulated by miRNA-584. The overexpression of LPIN1 accelerated OCa cells to proliferate and migrate. Importantly, LPIN1 was responsible for OCa progression regulated by miRNA-584. CONCLUSIONS: MiRNA-584 is downregulated in OCa tissues and cell lines. MiRNA-584 level is correlated with lymphatic metastasis, distant metastasis, and poor prognosis in OCa patients. By negatively regulating LPIN1, miRNA-584 suppresses the malignant progression of OCa.

[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.

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD.

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298-8.284; P=0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.

Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine.

Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challenge in a rhesus macaque model. Both the DNA and rMVA components of the vaccine expressed multiple immunodeficiency virus proteins. Two DNA inoculations at 0 and 8 weeks and a single rMVA booster at 24 weeks effectively controlled an intrarectal challenge administered 7 months after the booster. These findings provide hope that a relatively simple multiprotein DNA/MVA vaccine can help to control the acquired immune deficiency syndrome epidemic.

[Vaccine loss related to the expanded immunization program in Xinjiang Uygur Autonomous Region, 2016-2017].

Objective: To assess the vaccine loss related to the Expanded Program on Immunization (EPI) in Xinjiang Uygur Autonomous Region so as to improve the management of vaccines. Methods: A total of 135 vaccination clinics were randomly selected, using a stratified cluster sampling method. In each clinic, data on vaccination was collected between 2016 and 2017, including the number of doses in routine immunization program and supplementary immunization activities (i.e., vaccine doses in vials that were opened for use) on polio vaccine, number of doses administered to children and the number of doses discarded (e.g., expired vaccine or broken vials that had not been opened for use), etc. Coefficient on vaccine loss was calculated with the following equation: vaccine loss coefficient=(number of vaccine doses used)/(number of vaccine doses administered). The vaccine discard rate appeared as: number of vaccine doses discarded)/number of vaccine doses used. Results: For vaccines in single-dose vials [diphtheria-tetanus-pertussis vaccine (DTaP) and trivalent oral polio virus vaccine (tOPV)], the loss coefficients appeared as 1.00 and 1.02, respectively. For vaccines in multi-dose vials [bivalent oral polio vaccine (bOPV), group A meningococcal polysaccharide vaccine (MPV-A), diphtheria-tetanus combined vaccine (DT) and bacilli Calmette-Guérin (BCG) vaccine], the loss coefficients were 1.58, 1.67, 1.68, and 3.02, respectively. The coefficients of EPI vaccine loss in urban, rural, and pastoral area vaccination clinics ranged between 1.00-2.84, 1.00-3.71, and 1.00-2.27, respectively. Loss coefficients ranged between 1.00-3.00, 1.00- 4.41, and 1.00-1.94, respectively, were seen in township clinics, village clinics, and decentralized vaccination clinics. Coefficients on larger vaccine loss were associated with longer intervals between clinic sessions and with fewer vaccinations administrations per day. Conclusions: In Xinjiang, coefficients on the loss of multi-dose EPI vaccines were high. The coefficients on loss were different from the levels of region and types of clinics, and time interval between clinic sessions. Programs on refining the management and distribution of EPI vaccines, to minimize the vaccine loss were recommended.