Effects of neonatal respiratory distress syndrome on thymus in 130 premature infants / 国际儿科学杂志

Objective:To investigate the effects of neonatal respiratory distress syndrome(NRDS)on thymus of premature infants.Methods:We collected baseline data from premature infants with gestational age of 28~32 weeks in neonatal intensive care unit of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2019 to December 31, 2019.The largest transverse diameter and the sagittal of thymus were measured by ultrasonography within 24 h of birth, then, the thymic index(TI)and thymic weight index(TWI)were calculated to assess the size of thymus.The preterm neonates were divided into NRDS group and non-NRDS group according to the diagnosic criteria of NRDS, and the two groups were then divided into antenatal corticosteroid administration(ACS)group and non-ACS group according to ACS exposure.We then compared the TI and TWI between these groups.Results:One hundred and sixty-three preterm neonates were enrolled in our study, including 98 NRDS preterm neonates and 65 non NRDS preterm neonates.After matching gestational age and birth weight of the preterm neonates from two groups, 65 preterm neonates with NRDS comprised the NRDS group, and 65 preterm neonates without NRDS served as controls.Preterm neonates in NRDS group had significantly smaller TI[(1.788 ± 0.803)cm 3 vs.(2.420±1.068)cm 3, t=3.818, P<0.01] and TWI[(1.278 ± 0.380)cm 3/kg vs.(1.695 ± 0.491)cm 3/kg, t=5.401, P<0.01] than those in non-NRDS group.Besides, preterm neonates in NRDS group had smaller lymphocytes count[(3.729 ± 1.263)×10 9/L vs.(4.437 ± 1.608)×10 9/L, t=2.789, P<0.01] than that in non-NRDS group.For NRDS preterm neonates, TI[(1.487 ± 0.515)cm 3 vs(2.185 ± 0.942)cm 3, t=3.542, P<0.01] ]and TWI[(1.134± 0.311)cm 3/kg vs(1.469± 0.385)cm 3/kg, t=3.882, P<0.01] in ACS group were significantly smaller than those in non-ACS group.For non-NRDS preterm neonates, TI and TWI in ACS group also were significantly smaller than those in non-ACS group( t=2.676、3.659, P<0.05). Conclusion:NRDS is associated with thymic involution of preterm neonates, and ACS exposure affected the size of thymic in premature infants.

A novel intranasal administration adenoviral vector-based platform for rapid COVID-19 vaccine development

The coronavirus SARS-CoV-2 has a severe impact on global public health, and the emerging variants threaten the efficacy of the circulating vaccines. Here, we report that a single vaccination with a non-replicating chimpanzee adenovirus-based vaccine against the SARS-CoV-2 Delta variant (JS1-delta) elicits potent humoral, cellular and mucosal immunity in mice. Additionally, a single intranasal administration of JS1-delta provides effective protection against the Delta (B.1.617.2) variant challenge in mice. This study indicates that chimpanzee adenovirus type 3 (ChAd3) derived vector represents a promising platform for antiviral vaccine development against respiratory infections and JS1-delta is worth further investigation in human clinical trials. HighlightsO_LIA new chimpanzee adenoviral vaccine against the SARS-CoV-2 Delta variant was developed. C_LIO_LIThe vaccine elicited potent humoral, cellular and mucosal immunity in mice. C_LIO_LIThe vaccine protected mice from the Delta variant challenge. C_LI

Increased neutralization of SARS-CoV-2 Delta variant by nanobody (Nb22) and the structural basis

Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% global population are still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a means of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system as well as stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2. Brief summaryNb22 exhibits ultrahigh potency against Delta variant in vitro and is exploited by crystal structural analysis; furthermore, animal study demonstrates high effectiveness in the treatment and short-term instantaneous prophylaxis in hACE2 mice via intranasal administration. HighlightsO_LINb22 exhibits ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). C_LIO_LIStructural analysis elucidates the ultrapotent neutralization of Nb22 against Delta variant. C_LIO_LINb22 demonstrates complete protection in the treatment of Delta variant infection in hACE2 transgenic mice. C_LIO_LIWe complete the proof of concept of STIP against SARS-CoV-2 using intranasal Nb22 with ultrahigh potency and long-lasting retention in respiratory system. C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/459055v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@144516corg.highwire.dtl.DTLVardef@3dc17forg.highwire.dtl.DTLVardef@6a8962org.highwire.dtl.DTLVardef@619cd7_HPS_FORMAT_FIGEXP M_FIG C_FIG

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

The dramatically expanding COVID-19 needs multiple effective countermeasures. Neutralizing antibodies are a potential therapeutic strategy for treating COVID-19. A number of neutralizing nanobodies (Nbs) were reported for their in vitro activities. However, in vivo protection of these nanobodies was not reported in animal models. In the current report, we characterized several RBD-specific Nbs isolated from a screen of an Nb library derived from an alpaca immunized with SARS-CoV-2 spike glycoprotein (S); among them, three Nbs exhibited picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and 15 circulating SARS-CoV-2 variants. To improve the efficacy, various configurations of Nbs were engineered. Nb15-NbH-Nb15, a novel trimer constituted of three Nbs, was constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibited sub-ng/ml neutralization potency against the wild-type and currently circulating variants of SARS-CoV-2 with a long half-life in vivo. In addition, we showed that intranasal administration of Nb15-NbH-Nb15 provided 100% protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both prevention and treatment of SARS-CoV-2 through respiratory administration. One sentence summaryNb15-NbH-Nb15, with a novel heterotrimeric bispecific configuration, exhibited potent and broad neutralization potency against SARS-CoV-2 in vitro and provided in vivo protection against SARS-CoV-2 infection in hACE2 transgenic mice via intranasal delivery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/429275v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@a30bc8org.highwire.dtl.DTLVardef@5a872eorg.highwire.dtl.DTLVardef@1610f74org.highwire.dtl.DTLVardef@13d9bd8_HPS_FORMAT_FIGEXP M_FIG Graphical abstract: C_FIG HighlightsO_LIWe described a novel heterotrimeric configuration of Nb-NbH-Nb (Nb15-NbH-Nb15) that exhibited improved viral inhibition and stability. C_LIO_LINb15-NbH-Nb15 provides ultrahigh neutralization potency against SARS-CoV-2 wild type and 18 mutant variants, including the current circulating variants of D614G and N501Y predominantly in the UK and South Africa. C_LIO_LIIt is the first to demonstrate the Nbs efficacy in preventing and treating SARS-CoV-2 infection in hACE2 transgenic mice via intranasal delivery. C_LI

Study on nurses scheduling based on multi-objective integer programming model in COVID-19 pandemic / 中华医院管理杂志

Objective:To establish a scientific and reasonable nurse scheduling model for ward nursing during COVID-19, to achieve collaborative and efficient scheduling of manpower and materials, and to provide an algorithm basis for the computerized scheduling as well as references for optimizing manpower scheduling in public health emergencies.Methods:The qualitative interview method was used to learn the challenges in nursing manpower scheduling at designated hospitals. In view of the nursing scheduling in the mild case wards during the pandemic and the premise of meeting the needs of different shift types and patient care, the goal was set as minimizing the consumption of nursing human resources and protective equipments. The objective functions, constraints and corresponding parameters were established. A multi-objective integer programming model was established by MATLAB software for solution by CPLEX solver.Results:Two objective functions, three hard constraints, two soft constraints and corresponding parameters were established. Calculations by the model so established found that a 28-day period requires at least 62 nurses, and at least 52 nurses in the contaminated wards, including 7 nurses in the department of intensive care, the infectious and the respiratory wards respectively. This number could meet in general the needs of epidemic care. In comparison, the manual scheduling of the mild care wards during the pandemic in February 2020 needed at least 69 nurses, and 61 in the contaminated wards, yet with a failure to meet all constraints.Conclusions:The model can solve the scheduling challenges in public health emergencies, namely numerous shift types, different nursing needs in different types of shifts, and complex staff structure.Furthermore, the model can save manpower and materials, serving a useful reference for manpower scheduling.

Application of PCR reverse dot blot in non-syndromic deafness gene detection / 临床耳鼻咽喉头颈外科杂志

Objective@#To detect 20 common deafness gene mutations in non- syndromic deafness patients in China using PCR- RDB, and analyze and summarize the mutation data to explore the clinical value of this method. @*Method@#The PCR- RDB and Sanger sequencing were used to detect 20 common mutations of four deafness genes（GJB2, GJB3, SLC26A4 and mtDNA） in 500 patients with non- syndromic hearing loss . The Sanger sequencing was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the deafness mutation detected by PCR- RDB. @*Result@#A total of 500 samples were detected. 147 wild- type samples, 81 homozygous mutant samples, 240 heterozygous mutant samples, 32 composite heterozygous mutant samples were detected using the PCR- RDB within the range of 20 gene mutations, which were identical to the Sanger sequencing results. GJB2 c.235delC and SLC26A4 c.919- 2 A>G are the most common hotspot mutations in this study, followed by mtDNA m. 1555 A>G. Compared with the Sanger sequencing method, the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the real- time fluorescence PCR melting curve method were 100%, and the Kappa value was one. @*Conclusion@#PCR reverse dot-blot hybridization is a simple, rapid, sensitive and specific method for detecting 20 mutations of 4 common deafness genes in Chinese population, it is expected to be used in clinical detection of deafness genes in the future.

Premature infant born to a convalescent mother with COVID-19 in mid-term pregnancy / 中华围产医学杂志

We report a female infant born preterm to a woman at 35 gestational weeks and four days in a normal pregnancy prior to delivery, with normal liquor volume and good maternal and infant outcomes. The baby was transferred to the neonatal department 30 min after birth at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, on March 21, 2020. The infant weighed 2 800 g with 7 and 9 Apgar scores respectively at 1 and 5 min. The mother had been diagnosed with COVID-19 at 26 +6 weeks of pregnancy and the maternal serum level of IgM was negative and that of IgG was 20.77 AU/ml (normal reference <10 AU/ml) before delivery. The baby had hypoglycemia on admission, and the blood sugar stabilized after treatment. Though early mild feeding intolerance occurred, the baby was able to feed normal by eight days after birth. The baby was in good condition during hospitalization and discharged. Throat swab specimens obtained from the infant on the 2nd, 3rd and 8th day after birth for SARS-Cov-2 RNA detection were all negative. On the 2nd and 8th day after birth, SARS-Cov-2 IgM in the neonatal serum were negative, while elevated IgG levels of 30.2 AU/ml and 25.3 AU/ml (normal reference value <10 AU/ml) were observed, suggesting that the infant's IgG antibody of SARS-CoV-2 may have come from the mother. According to this case report, no intrauterine vertical transmission was found in the pregnancy with SARS-CoV-2 infection in the second trimester, while further follow-up is still needed.

Effects of co-exposure of fluorine and arsenic on protein expression of TRAF-6-mediated NF-κB1 signaling pathway in osteoblasts and osteoclast co-culture systems / 中华地方病学杂志

Objective:To investigate the effects of combined exposure of fluorine, arsenic, and fluorine-arsenic on the signaling pathway related protein expression of tumor necrosis factor receptor-related factor 6 (TRAF-6)/nuclear factor κB1(NF-κB1) in a co-culture system of mouse osteoblasts MC3T3-E1 and mouse monocyte macrophage RAW264.7.Methods:MC3T3-E1 cells were co-cultured with RAW264.7 cells after induction with osteogenic inducers. The cells were cultured for 7 days in vitro, and different doses of sodium fluoride (0.0, 0.1, 0.4, 1.6 mmol/L NaF, F), sodium arsenite (0.0, 0.5, 2.5, 12.5 μmol/L NaAsO 2, As) and different doses of fluorine and arsenic were added to the culture medium and cultured for 24 h using factorial design. The expression levels of nuclear factor κB receptor activating factor (RANK), TRAF-6, NF-κB1, T cell activating factor (NFATc1), and tartrate-resistant acid phosphatase (TRAP) protein were detected by Western blotting. Results:When fluorine was used alone, compared with the control group (F 0.0As 0.0, 1.00 ± 0.00), the expressions of RANK, NF-κB1 and TRAP proteins (1.11 ± 0.04, 1.29 ± 0.05, 1.38 ± 0.04, 1.24 ± 0.04, 1.13 ± 0.03, 1.34 ± 0.05, 1.12 ± 0.03, 1.24 ± 0.04, 1.61 ± 0.06) were increased ( P < 0.05); TRAF-6 protein expressions in F 0.1 and F 1.6 groups (1.23 ± 0.04, 1.35 ± 0.03) were increased ( P < 0.05). When arsenic was used alone, compared with the control group (F 0.0As 0.0), the expressions of RANK, TRAF-6, NF-κB1 proteins were increased in As 0.5 group ( P < 0.05), the expressions of RANK and NFATc1 proteins were reduced in As 12.5 group ( P < 0.05). When fluorine was combined with arsenic, at the same dose of fluorine, RANK protein expression in F 0.1As 0.5 group and TRAF-6 protein expression in F 0.1As 12.5, F 0.4As 0.5, F 0.4As 2.5 groups, NF-κB1 protein expression in F 0.1As 0.5 F 0.4As 2.5, F 0.4As 12.5 groups, NFATc1 protein expression in F 0.1As 0.5 and F 0.4As 0.5 groups, TRAP protein expression in F 0.1As 12.5 group were higher than the corresponding fluorine groups alone (F 0.1, F 0.4, P < 0.05), but lower than the sum of fluorine and arsenic alone. At the same dose of arsenic, RANK protein expression in F 0.1As 12.5 group, TRAF-6 protein expression in F 0.1As 12.5 and F 0.4As 2.5 groups, and NF-κB1 protein expression in F 0.1As 12.5, F 0.4As 2.5, F 0.4As 12.5, and F 1.6As 2.5 groups, TRAP protein expression in F 1.6As 2.5 and F 1.6As 12.5 groups were higher than the corresponding arsenic groups alone (As 2.5, As 12.5, P < 0.05), but lower than the sum of fluorine and arsenic alone. Fluorine had a major effect on the expressions of RANK, TRAF-6, NF-κB1, NFATc1, and TRAP proteins ( F=3.41, 341.73, 66.01, 56.49, 147.40, P < 0.05); arsenic also had a main effect on all protein indicators ( F=686.71, 174.96, 107.32, 235.80, 331.37, P < 0.05); the combined effect of fluorine and arsenic had an interaction effect on each protein indicator ( F=50.39, 234.94, 116.72, 67.77, 36.56, P < 0.05). Conclusions:In the co-culture system of MC3T3-E1 and RAW264.7 cells, fluorine can activate TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins, thereby promoting osteoclast differentiation; the effects of arsenic on the expression of related proteins are not completely consistent. The interaction of fluorine and arsenic exposure on TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins is mainly antagonistic.

Application of PCR reverse dot blot in non-syndromic deafness gene detection / 临床耳鼻咽喉头颈外科杂志

To detect 20 common deafness gene mutations in non- syndromic deafness patients in China using PCR- RDB, and analyze and summarize the mutation data to explore the clinical value of this method. The PCR- RDB and Sanger sequencing were used to detect 20 common mutations of four deafness genes（, and ） in 500 patients with non- syndromic hearing loss . The Sanger sequencing was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the deafness mutation detected by PCR- RDB. A total of 500 samples were detected. 147 wild- type samples, 81 homozygous mutant samples, 240 heterozygous mutant samples, 32 composite heterozygous mutant samples were detected using the PCR- RDB within the range of 20 gene mutations, which were identical to the Sanger sequencing results. GJB2 c.235delC and SLC26A4 c.919- 2 A>G are the most common hotspot mutations in this study, followed by mtDNA m. 1555 A>G. Compared with the Sanger sequencing method, the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the real- time fluorescence PCR melting curve method were 100%, and the Kappa value was one. PCR reverse dot-blot hybridization is a simple, rapid, sensitive and specific method for detecting 20 mutations of 4 common deafness genes in Chinese population, it is expected to be used in clinical detection of deafness genes in the future.

Application of the real-time fluorescence PCR melting curve method in gene screening of non-syndromic hearing loss / 中华耳鼻咽喉头颈外科杂志

Objective@#To detect 20 common deafness gene mutations in non-syndromic hearing loss patients in China using the melting curve method, and analyze and summarize the mutation data to explore the clinical value of this method.@*Methods@#The real-time fluorescence PCR melting curve method was used to detect 20 common mutations of four deafness genes(GJB2,GJB3,SLC26A4 and mtDNA) in 492 patients with non-syndromic hearing loss recruited between March 2014 and September 2016 from the Otolaryngology Department of Xiangya Hospital, Central South University(283 males and 209 females, the age ranged from 1 to 48 years old). The Sanger sequencing method was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the deafness mutation detected by the real-time fluorescence PCR melting curve method.@*Results@#A total of 492 samples were detected. 193 wild-type samples, 93 homozygous mutant samples, 145 heterozygous mutant samples, 59 composite heterozygous mutant samples and 2 samples with unknown mutations were detected using the real-time fluorescence PCR melting curve method within the range of 20 gene mutations, whichwere identical to the Sanger sequencing results.The two samples were detected as unknown mutations by the real-time fluorescent PCR melting curve method were confirmed by Sanger sequencing, including a composite heterozygous mutant sample and a homogenous mutation sample. GJB2 c.235delC and SLC26A4 c.919-2 A>G were the most common hotspot mutations in this study, followed by mtDNA m.1555 A>G. Compared with the Sanger sequencing method, the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the real-time fluorescence PCR melting curve method were 100%, the Youden′s index was 1.0, and the Kappa value was 1.@*Conclusions@#The real-time fluorescence PCR melting curve method is suitable for the detection of deafness gene mutations. It has the advantages in terms of simple, rapid, high sensitivity and strong specificity and can accurately detect the 20 gene mutations of 4 common deafness genes in Chinese population, which is expected to be used for the clinical detection of deafness genes in the future.

Diagnostic value of contrast-enhanced ultrasound for dysplastic nodule with a focus of hepatocellular carcinoma / 中华超声影像学杂志

Objective To investigate the imaging features of dysplastic nodules with a focus of hepatocellular carcinoma ( DN-HCC ) on contrast-enhanced ultrasound ( CEUS ) and to improve the diagnostic accuracy . Methods The clinical data of 60 patients and CEUS imaging of 62 hepatic nodules [DN-HCCs , n =54 ;dysplastic nodules (DN) , n =8] pathologically proved were reviewed retrospectively . According to Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) , the lesions were categorized . Results Significantly different CEUS patterns between DN-HCCs and DNs were observed ( P < 0 .05) . During the arterial phase ,54 DN-HCC lesions showed various enhancement patterns [ hypervascular ,59 .3％ ( 32/54 ) ;nodule-in-nodule ,9 .3％ ( 5/54 ) ;isovascular ,13 .0％ ( 7/54 ) and hypovascular ,18 .5％ (10/54)] . Of the 54 DN-HCC lesions ,44 .4％ (24/54) showed washout during the late phase .Of the 8 DN lesions ,62 .5％ (5/8) showed iso-enhancement during the arterial phase ,25％ (2/8) showed hypo-enhancement ,and 12 .5％ (1/8) showed hyper-enhancement . No DN lesion showed washout during the late phase .According to CEUS LI-RADS (LR) algorithm ,27 .8％ (15/54) DN-HCCs were LR-5 ,46 .3％ (25/54) DN-HCCs were LR-4 ,25 .9％ (14/54) DN-HCCs and 100％ (8/8) DNs were LR-3 . Regarding hyper-enhancement ( including local hyper-enhancement ) during the arterial phase or hypo-enhancement (including local hypo-enhancement) during the late phase as the diagnostic standard of DN-HCC , the diagnostic sensitivity , specificity and accuracy value were 83 .3％ , 87 .5％ and 83 .9％ , respectively . Conclusions The imaging features of hyper-enhancement during the arterial phase or hypo-enhancement during the late phase on CEUS are useful to diagnose DN-HCCs .

Expression of PD-L1 and its prognostic role in patients with esophageal squamous cell carcinoma / 临床与实验病理学杂志

Purpose To analyze the correlations between PD-L1 expression and clinicopathological factors and their prognostic values in esophageal squamous cell carcinoma (ESCC) patients.Methods PD-L1 expression in the primary tumors from 253 patients with ESCC was evaluated using tissue microarray and immunohistochemistry (IHC).PD-L1 positivity was defined as positive staining of 1％ and 5％ tumor cells.Survival curves were constructed by using the Kaplan-Meier method.Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results Overall,tumoral PD-L1 expression was potentially associated with favorable DFS and OS.When the patients were stratified into stage Ⅰ + Ⅱ (60.9％,154/253) and stage Ⅲ + Ⅳa (39.1％,99/253),the prognostic role was not consistent.In patients with stage Ⅰ + Ⅱ disease,tumoral PD-L1 expression was associated with better DFS and OS upon multivariate analysis (1％ as the cutoff:P =0.046 and 0.021,5％ as the cutoff:P=0.011 and0.004).However,PD-L1 expression was not correlated with prognosis in patients with stage Ⅲ + Ⅳa disease (1％ as the cutoff:P =0.586 and 0.682,5％ as the cutoff:P =0.807 and 0.620).Conclusion The prognostic role of tumoral PDL expression is variable in different stages of ESCC,and tumoral PDL expression is an independent favorable predictor in ESCC patients with Stage Ⅰ-Ⅱ disease,but not in stage Ⅲ-Ⅳa or lymph node metastasis.

HER-2 gene amplification and protein expression in esophageal squamous cell carcinoma / 临床与实验病理学杂志

To explore the status of HER-2 gene amplification and protein expression in Chinese esophageal squamous cell carcinoma patients and its relationship with the clinicopathological parameters.Methods The HER-2 gene amplification was detected by FISH and protein expression by IHC in 96 patients with esophageal squamous cell carcinoma that would be followed up for 3 years.Results Three cases presented with 3 +,15 cases with 2 +,11 cases with 1 +,and 67 with negative by HER-2 immunohistochemical staining;2 of 3 cases presented with HER-2 amplification in in 3 +,1 case presented with over 6 HER-2 copy numbers.HER-2 amplification and HER-2 overexpression had significant correlation (P ＜ 0.000 1).HER2 amplification or overexpression was associated with clinicopathological parameters,such as,carcinomas without necrosis (P =0.012) and lower stage (P =0.040).There was better DFS or OS trend in patients with HER-2 overexpression or amplification,but the significant difference did not reached.Conclusion This research has demonstrated the correspondence between gene amplification and protein overexpression of HER-2 in ESCC.HER-2 gene overexpression or amplification is a potential better predictive parameter in ESCC,but needs further study.

Early esophageal cancer or precancerous lesions treated by endoscopic resection: a single-center retrospective study of 368 cases / 临床与实验病理学杂志

To investigate the clinicopathological features as well as prognosis of early esophageal squamous cell neoplasm (ESCN) treated with endoscopic resection (ER).Methods 368 patients were collected from 2007 to 2013.Clinicopathological features including invasion depth and margin were evaluated.Survival curves were constructed by using the Kaplan-Meier method.Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results There were 252 males and 116 females with a median age of 61 (16-84) years.Patient numbers of hyperplasia,low grade intraepithelial neoplasia,high grade intraepithelial neoplasia,m1,m2,m3,sm1 and sm2 were 47(12.8％),61 (16.6％),61 (16.6％),54(14.7％),38(10.3％),63(17.1％),12(3.3％) and 32(8.7％),respectively.The cumulative overall 1-year,3-year,and 5-year rates of survival in the metachronous esophageal lesions were 4.1％,12.9％ and 32.6％,respectively.The incidence of lymph node/distant metastasis was 1.54％ in m3,6.25％ in sm2,and 0 in other subgroups.The overall 1-year,3-year,and 5-year survival rates were 99.5％,97.3％,and 87.5％,respectively.Significant difference was identified between sm2 and non-sm2 patients in metastatic rate (P =0.021),however,no significant difference existed between m3 patients and sm2 patients (P =0.252).Metachronous esophageal lesion and survival between sm2 and non-sm2 patients demonstrated no statistical difference (P =0.401 and P =0.634).Conclusion ER is an effective and relatively safe treatment for superficial ESCN.The procedure is still appropriate in selecting sin2 patients.It is necessary to monitor the second primary cancer in sm2 patients during follow-up.

Study of gene mutation and pathogenetic mechanism for a family with Waardenburg syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome.</p><p><b>METHODS</b>Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively.</p><p><b>RESULTS</b>A heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITFand mutant MITFwere confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm.</p><p><b>CONCLUSION</b>The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.</p>

Prevalence and Risk Factors of Mild Cognitive Impairment in Old People in Pension Facilities in Chongqing, China / 中国康复理论与实践

@#Objective To investigate the prevalence status and risk factors of mild cognitive impairment (MCI) in old people in pension facilities in Chongqing, China. Methods From October to November, 2015, the people above 60 years old in four pension facilities in Chongqing were cluster sampled. They were interviewed with Mini-Mental State Examination, Instrumental Activity of Daily Living Scale, self-made general situation questionnaire for the elderly and the Geriatric Depression Scale. Results There were 25 MCI patients identified in 84 old people selected, with the prevalence of 29.76%. MCI prevalence was different with the factors such as genders, educational levels, economical status, smoking, eating freshwater fish frequently, participating in outdoor activities frequently, playing Mahjong/chess/cards fre-quently, watching TV/listening to broadcast/reading newspaper frequently, participating in social activities frequently, having religious be-liefs, suffering high blood pressure (χ2>4.271, P<0.05). Based on multivariate Logistic regression analysis, male was the protective factor (OR=0.055, 95%CI:0.005~0.618), while high blood pressure was the risk factor (OR=8.281, 95%CI:1.278~53.646) to the MCI. Conclu-sion MCI is prevalent in old people in pension facilities in Chongqing, which needs intervention targeted to the risk foctors.

Alterations of dendritic cells, inflammatory monocytes and macrophages in mice during Pneumocystis ;murina infection / 中华微生物学和免疫学杂志

Objective To investigate the alterations and phenotypes of dendritic cells, inflamma-tory monocytes and macrophages in immunocompetent mice during Pneumocystis murina ( P.murina) infec-tion for further analysis of the function of these cells during P.murina infection.Methods Wild type male C57BL/6 mice at age 6-8 weeks were randomly divided into two groups including the group with P.murina infection and the group receiving sham surgery.The mice without any intervention were used to set up the blank control group.The loads of P.murina strains in lung tissues of each mouse were quantified by TaqMan real-time fluorescence polymerase chain reaction after the infection.Histopathological examination was per-formed to evaluate the degree of inflammation in lung tissues.The numbers of dendritic cells, inflammatory monocytes and macrophages in lung tissues, peripheral blood and bone marrow samples, and the changes of inflammatory monocytes in spleen tissues were measured by flow cytometry analysis.The expression of major histocompatability complexⅡ(MHCⅡ), CX3C chemokine receptor 1 (CX3CR1) and CC chemokine re-ceptor 2 ( CCR2 ) by dendritic cells, inflammatory monocytes and macrophages in lung tissues during P.murina infection were analyzed by flow cytometry analysis.All of the data were collected one, two, three and four weeks after the corresponding treatments.Results The loads of P.murina strains in P.murina in-fected mice were elevated after two and three weeks infection, but decline at week 4 (P>0.05).Significant pathological changes including the alveolar destruction, inflammatory cell infiltration and thickened alveolar septum in mice with P.murina infection were observed under a microscope at week 3 and week 4.Compared to the sham surgery treatment group, the number of CD11c+CD11b+dendritic cells were increased in lung tissues, but decreased in blood samples during P.murina infection ( P0.05).The CD11c+CD11b+dendritic cells in lung tissues of mice with P.murina infection expressed high levels of MHCⅡand CX3CR1, and low levels of CCR2.The inflammatory monocytes in lung tissues of mice expressed high levels of CCR2, moderate levels of MHCⅡand low levels of CX3CR1 during P.murina in-fection.High levels of CX3CR1 and low levels of MHCⅡ and CCR2 were observed in macrophages from lung tissues of mice with P.murina infection.Conclusion Highly expressed CD11c+CD11b+dendritic cells and MHCⅡwere detected in lung tissues of mice during P.murina infection, indicating that CD11c+CD11b+dendritic cells were involved in the host defense against P.murina infection.

Analysis of health self-management for diabetes self-efficacy / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of health self-management on self-efficiency of diabetes patients.
@*METHODS@#A total of 184 eligible and voluntary diabetes patients were recruited for 6 consecutive weeks of knowledge and skills intervention, and interviewed with questionnaire by diabetes self-efficacy scale (DSES) before and after the intervention. The changes in self-efficiency were compared with two paired sample McNemar test.
@*RESULTS@#After the intervention, the total scores of self-efficiency on diet, medication, blood sugar monitoring, foot care and complications management were all increased significantly compared with those before the intervention (P<0.05).
@*CONCLUSION@#The intervention model of health self-management for self-efficiency in diabetes patients is effective, and the quality of patients' life can be improved.

[Progress in the study of syndromic hearing loss resulted from neural crest abnormalities].

More than 400 types of syndromic hearing loss (SHL) have been reported so far, in which Waardenburg syndrome (WS), congenital microtia syndrome (CMS), and large vestibular aqueduct syndrome (LVAS) are the most common ones in clinic. However, it is difficult to study the genetic basis and pathogenesis of SHL in a systematical way because of the strong clinical and genetic heterogeneity of SHL. Dysfunction of neural crest cells (NCC), which are caused by the gene interaction network extended from SOX10 and PAX3, are relevant to the phenotype of WS, CMS and LVAS. Our previous study also confirmed that the gene network was involved in the pathogenesis of WS. In this review, we summarize research progress in the pathogenic mechanisms of SHL resulted from defects in neural crest decelopment, and provide the gene interaction network of neural crest abnormalities resulting in SHL, and hope to provide research ideas and theoretical basis for the systematical study on pathogenesis of common SHL.

Clinical Features of Eosinophilic Gastroenteritis / 胃肠病学

Background:The clinical presentation of eosinophilic gastroenteritis( EG)is nonspecific and has not received much concern by physicians and pathologists. The diagnosis of EG was delayed in many cases. Aims:To explore the clinical features of EG. Methods:The clinical,laboratory,endoscopic and radiologic features and treatment in patients who were diagnosed as EG from October 2011 to September 2013 in Zhongshan Hospital, Fudan University were analyzed retrospectively. Results:Median age of 10 EG patients was 41. 9 years. Four patients had a history of allergy or asthma. The time from onset to diagnose was 25 days on average. The most common symptoms were abdominal pain with bloating, diarrhea or vomiting. Eight patients had hypereosinophilia. Abdominal CT revealed uniform edema or stratified thickness of intestinal wall or ascites in 7 patients. Endoscopy revealed erythema,edema and erosion in antrum,duodenum or jejunum in 6 patients. All cases were confirmed as having eosinophilic infiltration by mucosal biopsy or examination of ascites. Seven patients were successfully treated with corticosteroid. One patients experienced relapse after discontinuing corticosteroids during following up. Conclusions:EG may be more common than previously recognized and should be considered in the differential diagnosis of unexplained abdominal pain with peripheral eosinophilia or uniform edema or stratified thickness of intestinal wall. Multiple biopsies in multiple sites including descending duodenum and pathological examination for finding eosinophil infiltration are the keys to confirm the diagnosis. Corticosteroids are effective in relieving symptoms and improving eosinophilia.