[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

[Clinical efficacy of femoral neck screw system combined with supported hollow screw in treatment of femoral neck fractures with posterometral comminution in young and middle-aged patients].

Objective: To investigate the clinical efficacy of dynamic cross screw system (FNS) for femoral neck fractures in young and middle-aged patients with posterior medial comminution. Methods: A retrospective cohort study. Clinical data of 197 young and middle-aged patients with femoral neck fractures accompanied by posterior medial comminution treated with closed reduction FNS and internal fixation with anti-rotation cannulated screws in Beijing Luhe Hospital, Beijing Jishuitan Hospital and Beijing Tongren Hospital from October 2019 to October 2021 were analyzed retrospectively. According to different surgical methods, the patients were divided into two groups. There were 102 patients in the FNS group, included 55 males and 47 females with a mean age of (40.49±19.79) years; and there were 95 patients in the FNS plus anti-rotation hollow screw group (combined group), included 51 males and 44 females with an average age of (40.03±18.82) years. All patients were followed-up for at least 1 year after surgery. The general clinical data, surgical conditions and Harris score of the hip joint at the last follow-up of the two groups were compared. And the clinical efficacy of the two surgical schemes were evaluated and compared. After surgery, routine X-ray and CT examinations were performed to evaluate the fracture reduction and internal fixation, and the shortening of the femoral neck on the affected side was compared to that of healthy side according to the Zlowodzki method. Results: At the last follow-up, the incidence of fracture reduction loss, screw resection and coxa vara in the combined group were all significantly lower than those in the FNS group [10 (10.5%) vs 28 (27.4%), 1 (1.0%) vs 7 (6.8%) and 9 (9.4%) vs 21 (20.5%), respectively, all P<0.05]. The incidence of nonunion and necrosis of the femoral head in the combined group were both lower than those in the FNS group, but there was no significant difference between two groups (both P>0.05). The postoperative mild, moderate and severe femoral neck shortening in the combined group were all lower than those in the FNS group, and the difference were not statistically significant (all P>0.05). At the last follow-up, the Harris score in the combined group was 84.60±2.08, and it was higher than that in the FNS group (79.57±4.31), but the difference was not statistically significant (P=0.403). Conclusion: FNS plus supporting hollow screw has a good clinical effect on femoral neck fractures in young and middle-aged adults with posterior medial comminution.

[Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia].

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

First report of Fusarium incarnatum causing spikelet rot on rice in China.

Rice (Oryza sativa L.) is the most important and widely grown crop, covering about 29.9 million ha of total cultivation area in China. In the last decade, spikelet rot disease on rice became much more frequent in the middle and lower reaches of the Yangtze River, China. Fusarium proliferatum (Matsush.) Nirenberg ex Gerlach & Nirenberg was reported to be a causal agent of spikelet rot on rice in Hangzhou, Zhejiang province (Huang et al. 2012). In September 2019, a survey was conducted to understand the etiology of the disease in the main rice growing regions of Jinshan District of Shanghai. Symptomatic panicles exhibiting reddish or brown discoloration on the glumes were collected from different rice fields, where disease incidence was estimated to be between 20 to 80%. Diseased glumes were cut into small sections (5 × 5 mm) from the boundary of necrotic and healthy tissues, surface-sterilized with 75% ethanol for 30 s and 3% sodium hypochlorite for 90 s, rinsed twice with sterile distilled water, then placed onto 1/5 strength potato dextrose agar (PDA). After 3 to 5 days of incubation at 28°C in the dark, fungal growth with Fusarium-like colonies were transferred to PDA and purified by the single-spore isolation method. A total of 12 isolates were obtained and colonies showed loosely floccose, white mycelium and pale-yellow pigmentation on PDA. Microconidia were ovoid mostly with 0 to 1 septum, and measured 4.2 to 16.6 × 2.5 to 4.1 µm (n = 50). After 5-7 days of inoculation on carnation leaf agar (CLA), macroconidia produced usually had 3 to 5 septa, slightly curved at the apex, ranging from 15.7 to 39.1 × 3.3 to 5.0 µm (n = 50). Chlamydospores were produced in hyphae, most often solitary in short chains or in clumps, ellipsoidal or subglobose with thick and roughened walls. Molecular identification was performed on the representative isolates (JS3, JS9, and JS21). The rDNA internal transcribed spacer (ITS), translation elongation factor (TEF-1α) and ß-tubulin (ß-TUB) genes were amplified and sequenced using the paired primers ITS1/ITS4 (White et al. 1990), EF1/EF2 (O'Donnell et al. 1998) and T1/T22 (O'Donnell and Cigelnik 1997), respectively. The obtained sequences were deposited in GenBank under accession numbers MT889972 to MT889974 (ITS), MT895844 to MT895846 (TEF-1α), and MT895841 to MT895843 (ß-TUB), respectively. BLASTn search of the sequences revealed 99 to 100% identity with ITS (MF356578), TEF-1α (HM770725) and ß-TUB (GQ915444) of Fusarium incarnatum isolates. FUSARIUM-ID (Geiser et al. 2004) analysis showed 99 to 100% similarity with sequences of the F. incarnatum-equiseti species complex (FIESC) (FD_01651 and FD_01628). In addition, a phylogenetic analysis based on the concatenated nucleotide sequences placed the isolates in the F. incarnatum clade at 100% bootstrap support. Thus, both morphological observations and molecular criteria supported identification of the isolates as F. incarnatum (Desm.) Sacc (synonym: Fusarium semitectum) (Leslie and Summerell 2006, Nirenberg 1990). Pathogenicity tests were performed on susceptible rice cultivar 'Xiushui134'. At pollen cell maturity stage, a 2-ml conidial suspension (5 × 105 macroconidia/ml) of each isolate was injected into 10 rice panicles. Control plants were inoculated with sterile distilled water. Then, the pots were kept in a growth chamber at 28°C, 80% relative humidity, and 12 h/12 h light (10,000 lux)/dark. The experiment was repeated two times for each isolate. Two weeks post-inoculation, all inoculated panicles showed similar symptoms with the original samples, whereas no symptoms were observed on the control. The pathogen was re-isolated from inoculated panicles and identified by the method described above to fulfill Koch's postulates. Previous studies reported that F. incarnatum reproduced perithecia to overwinter on rice stubble as the inoculum of Fusarium head blight of wheat in southern China (Yang et al. 2018). To our knowledge, this is the first report of spikelet rot on rice caused by F. incarnatum in China. Further investigation is needed to gain a better understanding its potential geographic distribution of this new pathogen on rice crop. References: (1) Huang, S. W., et al. 2011. Crop Prot. 30: 10. (2) White, T. J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA. (3) O'Donnell, K., et al. 1998. Proc. Natl. Acad. Sci. U.S.A. 95: 2044. (4) O'Donnell, K., Cigelnik, E. 1997. Mol. Phylogenet. Evol. 7: 103. (5) Geiser, D. M., et al. 2004. Eur. J. Plant Pathol. 110: 473. (6) Leslie, J. F., and Summerell, B. A. 2006. The Fusarium Laboratory Manual. Blackwell, Ames, IA. (7) Nirenberg, H. I. 1990. Stud. Mycol. 32: 91. (8) Yang, M. X., et al. 2018. Toxins. 10: 115. The author(s) declare no conflict of interest. Funding: Funding was provided by National Natural Science Foundation of China (grant no. 31800133), Zhejiang Provincial Natural Science Foundation of China (grant no. LQ18C140005), Key Research and Development Program of Zhejiang Province (grant no. 2019C02018), Shanghai Science and Technology for Agriculture Promotion Project (2019-02-08-00-08-F01127), and the Agricultural Science and Technology Innovation Program of China Academy of Agricultural Science (CAAS-ASTIP-2013- CNRRI).

[Alteration on hepatocyte nuclear factor 1α expressions and significance in the process of occurrence and development of liver inflammation and fibrosis in patients with chronic hepatitis B].

Objective: To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B. Methods: Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ(2) test was used for bidirectional ordered grouping data, and Spearman's rank-correlation test was used for rank correlation analysis. Results: There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues (χ (2)(MH) = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade (r(s) = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis (χ (2)(MH) = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage (r(s) = -0.713, P < 0.05). Conclusion: HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

Identification, genealogical structure and population genetics of S-alleles in Malus sieversii, the wild ancestor of domesticated apple.

The self-incompatibility (SI) gene that is specifically expressed in pistils encodes the SI-associated ribonuclease (S-RNase), functioning as the female-specificity determinant of a gametophytic SI system. Despite extensive surveys in Malus domestica, the S-alleles have not been fully investigated for Malus sieversii, the primary wild ancestor of the domesticated apple. Here we screened the M. sieversii S-alleles via PCR amplification and sequencing, and identified 14 distinct alleles in this species. By contrast, nearly 40 are present in its close wild relative, Malus sylvestris. We further sequenced 8 nuclear genes to provide a neutral reference, and investigated the evolution of S-alleles via genealogical and population genetic analyses. Both shared ancestral polymorphism and an excess of non-synonymous substitution were detected in the S-RNases of the tribe Maleae in Rosaceae, indicating the action of long-term balancing selection. Approximate Bayesian Computations based on the reference neutral loci revealed a severe bottleneck in four of the six studied M. sieversii populations, suggesting that the low number of S-alleles found in this species is mainly the result of diversity loss due to a drastic population contraction. Such a bottleneck may lead to ambiguous footprints of ongoing balancing selection detected at the S-locus. This study not only elucidates the constituents and number of S-alleles in M. sieversii but also illustrates the potential utility of S-allele number shifts in demographic inference for self-incompatible plant species.

Baseline antibody level may help predict the risk of active human cytomegalovirus infection in a HCMV seropositive population.

Recurrent human cytomegalovirus (HCMV) infection during pregnancy could lead to congenital HCMV infection and permanent sequelae. However, knowledge regarding the risk factors associated with recurrent HCMV infection is limited. In the present study, 1,659 paired serum samples from the natural population were collected in Guangxi Province, China, from 2003 to 2004 with a 1-year interval. The serum anti-pp150 titre was quantitatively determined using a homemade recombinant pp150-based ELISA, and the IgG titre that increased at least 4-fold was defined as a recurrent infection. The HCMV seroprevalence was above 98.6% (1,636/1,659) in Guangxi in 2003, and the infection rate during the 1-year follow-up was approximately 10% (171/1,659). The seronegative population has the highest infection risk, while the risk of recurrent infection in the seropositive population was negatively correlated with the baseline anti-pp150 titre. With a cutoff of 1:80 (the baseline anti-pp150 IgG titre), the sensitivity and specificity were 73.1% (125/171) and 85.7% (1,275/1,488) respectively, and the relative risk of infection in the high-risk group compared to the low-risk group was 10.6 (95% CI: 7.7-14.6). In conclusion, the baseline anti-pp150 IgG was negatively correlated with the risk of HCMV infection and could be an excellent predictor of HCMV infection in HCMV seropositive populations.

Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015.

Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5' untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped. Twenty-two genotypes were identified. Enterovirus 71 (EV71) and coxsackieviruses A16, A6 and A10 (CA16, CA6 and CA10) were the most common genotypes, and there were no changes in the predominant lineages of these genotypes. EV71 became the most predominant genotype every 2 years. From 2013, CA6 replaced CA16 as one of the two most common genotypes. The results demonstrate the vast diversity of HFMD pathogens, and that minor genotypes are able to replace major genotypes. We recommend carrying-out long-term monitoring of the full spectrum of HFMD pathogens, which could facilitate epidemic prediction and the development of diagnostic assays and vaccines.

Effects of curcumin plus Soy oligosaccharides on intestinal flora of rats with ulcerative colitis.

To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay). Colonic tissues with the most obvious lesions were obtained using a surgical scissor. A routine hematoxylin-eosin (HE) staining method was used to stain pathological specimens and images of staining results were obtained. Histological injury scores of colonic mucosa were calculated. Ulcerative colitis model rats had the highest macroscopic damage scores and histological injury scores of colonic mucosa. After treatment the contents of TNF-α and IL-8 decreased significantly in the group of curcumin plus soy oligosaccharide compared with the model group with statistical significance (P <0.01) while the contents were close to those in the SASP group. There was no statistical significance (P> 0.05). The treatment could decrease TNF-α and IL- 8 expression and reduce colonic mucosa inflammation and tissue damage.

The prevalence of latent tuberculosis infection in rural Jiangsu, China.

OBJECTIVES: Diagnosis and interventional treatment of latent tuberculosis (TB) infection (LTBI) are important components in tuberculosis control. But systematic studies regarding the epidemic of LTBI are still rare in China. The objective of this study was to assess the prevalence and risk factors associated with LTBI based on the results of a domestic TB-specific gamma interferon (IFN-γ) release assay (TB-IGRA) in rural Jiangsu, China. STUDY DESIGN: Cross-sectional study of subjects registered in eight villages in Jiangsu, China. METHODS: This study was conducted in 2012 in eight villages. After recruitment, individuals with active TB or a history of TB were excluded. The TB-IGRA was performed for diagnosis of LTBI. RESULTS: 2169 of 2185 subjects met the requirement and were analysed in this study. 524 (24.3%) had a positive result, and positive rate gradually increased with age (P for trend <0.001). Multivariate analyses showed that increasing age, male gender and a history of TB exposure were risk factors associated with LTBI. Bacillus Calmette-Guérin (BCG) vaccination did not reduce the risk of TB infection in participants (aged ≥20 years). CONCLUSIONS: The findings of this study demonstrate that the prevalence of LTBI in China might be overestimated by tuberculin skin test compared with IFN-γ release assay (IGRA). The degree of TB exposure is related to Mycobacterium tubercuium (MTB) infection, and BCG vaccination offers little protection against MTB infection in adults. The early and effective detection and treatment of active TB patients, and screening and intervention for LTBI patients with a high risk of developing active TB could be cost-effective methods for TB control in China.

[The effects of different tidal volume ventilation on right ventricular function in critical respiratory failure patients].

Objective: To observe and explore the effects of different tidal volume (VT) ventilation on right ventricular (RV) function in patients with critical respiratory failure. Methods: Consecutive respiratory failure patients who were treated with invasive ventilator over 24 h in the Department of Critical Care Medicine at the Fourth Hospital of Hebei Medical University from June to December in 2015 were enrolled in this study.Clinical data including patients' vital signs, ventilator parameters and RV echocardiography were collected within 6 h (D0), day1(D1), day2 (D2) and day3 (D3) after ventilation started.According to the VT, patients with acute respiratory distress syndrome (ARDS) were assigned to low VT group [S6, ≤6 ml/kg predicted body weight (PBW)] and high VT group (L6, >6 ml/kg PBW), while non-ARDS patients were also assigned to low VT group (S8, ≤8 ml/kg PBW) and high VT group (L8, >8 ml/kg PBW). Results: A total of 84 patients were enrolled in this study.44.2% ARDS patients and 58.5% non-ARDS patients were in low VT groups.After ventilation, tricuspid annulus plane systolic excursion(TAPSE)decreased progressively in S6 [from 18.30(16.70, 20.70) mm to 17.55(15.70, 19.50) mm, P=0.001], L6 [from 19.50(17.00, 21.00) mm to 16.30(15.00, 18.00) mm P=0.001], S8[from 18.00(16.00, 21.00) mm to 16.50(15.50, 18.00) mm, P=0.001] and L8 [from 19.00(17.50, 21.50) mm to 16.35(15.15, 17.00) mm, P=0.001] groups.However, TAPSE decreased less in small VT groups (S6 and S8) than those of in large VT groups (S8 and L8) without significant differences.There were not statistical differences between different VT groups in terms of ventilation days, including right ventricle area/left ventricle area (RV(area)/LV(area)), TAPSE, peak mitral flow velocity of the early rapid filling wave (E), peak mitral flow velocity of the late rapid filling wave (A), early diastolic velocity of the tricuspid annulus (e'), pulmonary artery systolic pressure, inferior vena cava diameter (all P>0.05). Compared to L6 group, low VT (S6 group) resulted in decreased mortality at 28 days [1/19 vs 37.5%(9/24), P=0.014]. There were not statistical differences between different VT groups in terms of ventilation days, length of intensive care unit stay, length of hospital stay (all P>0.05). Logistic regression analysis showed that VT could be the independent factor of TAPSE (OR=1.104, 95%CI 0.100-1.003, P=0.049). Conclusions: Positive pressure mechanical ventilation resulted in RV systolic dysfunction .Lower VT may have the protective effect on RV function. Trial registration: Chinese Clinical Trial Registry, ChiCTR-POC-15007563.

Liver Transplantation in a Patient With CD40 Ligand Deficiency and Hyper-IgM Syndrome: Clinical and Immunological Assessments.

Monoclonal antibodies that disrupt CD40-CD40 ligand (CD40L) interactions are likely to have use in human transplantation. However, the extent of the immunosuppressive effects of CD40-CD40L blockade in humans is unknown. Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency syndrome characterized by defects in the CD40-CD40L pathway, severe immune deficiency (IgG), and high or normal IgM levels. However, the effects of CD40L deficiency on T- and natural killer (NK)-cell function is not established. Here, we present a patient with HIGM syndrome who underwent liver transplantation for hepatitis C virus infection. Posttransplantation, NK-cell antibody-dependent cytokine release (γ-interferon) to alloantigens and T cell responses to viral antigens and mitogens were assessed and showed normal CD4+ , CD8+ , and NK-cell responses. We also examined antibody-dependent cellular cytotoxicity against a CD40+ and HLA-expressing cell line. These experiments confirmed that the patient's NK cells were equivalent to those of normal subjects in mediating antibody-dependent cellular cytotoxicity despite the absence of CD40-CD40L interactions. Mitogenic stimulation of the patient's peripheral blood mononuclear cells showed no expression of CD40L on T and NK cells compared with increased expression in normal subjects. Taken together, these data suggest that absence of CD40L expression is responsible for aberrant B cell immunity but had little impact on NK- and T cell immune responses in vitro.

An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005 to 2011.

BACKGROUND: The prevalence of allergic rhinitis (AR) has increased worldwide in recent decades. This study was conducted to investigate the prevalence of self-reported AR and profiles of AR-related comorbidities in the adult population of China over time. METHODS: This study surveyed residents of 18 major cities in mainland China. Telephone interviews were conducted with study participants after sampling target telephone numbers by random digit dialing. The questions asked during telephone interviews were based on those included in validated questionnaires and focused on topics regarding AR, nonallergic rhinitis (NAR), acute/chronic rhinosinusitis (ARS/CRS), asthma, and atopic dermatitis (AD). RESULTS: During 2011, a total of 47 216 telephone interviews were conducted, and the overall response rate was 77.5%. When compared with the AR prevalence in 11 cities surveyed in 2005, there was a significant increase in self-reported adult AR in eight of those cities (P < 0.01). In 2011, the standardized prevalence of self-reported adult AR in the 18 cities was 17.6%. The concentration of SO2 was positively correlated with the prevalence of AR (r = 0.504, P = 0.033). A multiple regression model showed that the absolute change in household yearly income was significantly associated with the change in the prevalence of AR (R(2)  = 0.68), after adjusting for PM10 , SO2 , NO2, temperature, and humidity. The overall prevalences of NAR, ARS, CRS, asthma, and AD in the general population were 16.4%, 5.4%, 2.1%, 5.8%, and 14%, respectively. CONCLUSION: During a 6-year period, there was a significant increase in the prevalence of self-reported AR in the general Chinese adult population. The incidence of AR being accompanied by rhinosinusitis, asthma, or AD was significantly higher among individuals having self-reported AR compared with the general population.

The association between ankle-brachial index and asymptomatic cranial-carotid stenosis: a population-based, cross-sectional study of 5440 Han Chinese.

BACKGROUND AND PURPOSE: Routine screening for asymptomatic cranial-carotid stenosis (ACCS) is controversial and recommendation in clinical practice is vague. The ankle-brachial index (ABI) is reported as a predictor for cardiovascular disease. However, there is a scarcity of data about the association between abnormal ABI and ACCS. A population-based cross-sectional study was conducted to explore the relationship between ABI and ACCS. METHODS: A sample of 5440 Chinese adults aged 40-94 years old was recruited from 2010 to 2011. The ABI was measured using a portable Doppler device and ACCS was evaluated by bilateral carotid duplex ultrasound and portable examination devices. A logistic regression model was used to analyse the association between ABI and ACCS after adjusting for potential confounding factors. RESULTS: A low ABI was associated with ACCS [odds ratio (OR) 1.95, 95% confidence interval (CI) 1.42-2.67] after adjusting for potential confounders. When the data were stratified by age and sex, the correlation remained statistically significant in the male (OR 2.32, 95% CI 1.60-3.37) and elderly (OR 3.07, 95% CI 1.97-4.78) subgroups compared to the female (OR 1.26, 95% CI 0.67-2.39) and middle-aged groups (OR 1.27, 95% CI 0.77-2.12), respectively. CONCLUSION: This study demonstrated that low ABI is a significant risk factor for ACCS in male and elderly Chinese adults.

Effect of friction on vibrotactile sensation of normal and dehydrated skin.

BACKGROUND: Vibrotactile sensation mediated is highly dependent on surface mechanical and frictional properties. Dehydration of skin could change these properties. OBJECTIVES: To investigate the relationship between friction and vibrotactile sensation of normal and dehydrated skin. METHODS: Vibrations were firstly measured during surface exploration using a biomimetic sensor. Piglet skin was used as human skin model to study frictional properties for both normal and dehydrated skin using an atomic force microscope on nanoscale and a pin-on-disk tribometer on macroscale. Effect of vibrational frequency on friction and vibrotactile perception was also observed on nano and macro scale for normal and dehydrated skin. RESULTS: The result indicated that dehydrated skin was less sensitive than normal skin. The coefficient of friction of dehydrated skin is smaller than that of normal skin on both nano and macro scale. The coefficient of friction increases as increasing scanning frequencies. CONCLUSION: There is a positive correlation between coefficient of friction and vibrotactile sensation on nanoscale and macroscale.

miR-218 tissue expression level is associated with aggressive progression of gastric cancer.

The aim of the present study was to investigate the clinical significance of microRNA-218 (miR-218) in gastric cancer. We enrolled 112 patients having undergone surgery for gastric cancer between May 2008 and June 2014. Expression of miR-218 was determined by real-time quantitative reverse transcription-polymerase chain reaction. Survival curves were plotted using the Kaplan-Meier method and compared by the log-rank test. We found that miR-218 expression was significantly downregulated in gastric cancer tissues compared to adjacent normal tissues (P < 0.001). Low miR-218 expression was significantly associated with tumor differentiation (P < 0.001), depth of tumor invasion (P = 0.006), and tumor node metastasis stage (P < 0.001). Kaplan-Meier survival analysis revealed that patients with low miR-218 levels showed significantly lower 5-year overall survival than those demonstrating high expression (P = 0.04). Multivariate Cox regression analyses indicated that low miR-218 expression constitutes an independent molecular biomarker for prediction of poor overall survival of gastric cancer patients (hazard ratio = 3.187, 95% confidence interval = 1.551-8.365, P = 0.037). In conclusion, miR-218 was remarkably downregulated in gastric cancer tissues and may serve as a prognostic biomarker for patients suffering from this disease.

Ageing effects on the diameter, nanomechanical properties and tactile perception of human hair.

BACKGROUND: The typical changes to hair associated with ageing are greying, thinning, dryness and brittleness. Research on the influence of ageing on hair properties will enable a detailed understanding of the natural ageing process. METHODS: The studies were carried out using an SEM (scanning electron microscope), a TriboIndenter and an artificial finger. Three characteristic features of tactile perception that could reflect the perceptual dimensions of the fineness, roughness and slipperiness of hair were extracted. The influences of ageing on the diameter, surface topography, nanomechanical properties and tactile perception of hair were determined. RESULTS: In the three age group hair samples, the children's group hair samples have the smallest diameter. The hair cuticles in the children and young adult groups were relatively complete and less damaged than in the elderly group. The hardness and elastic modulus of the young adult group's hair samples were higher than those in the elderly and children's groups. For all groups, loss modulus E" was smaller than storage modulus E'. Vertical deviations (R) and coefficient of friction (µ) increased, and spectral centroid (SC) decreased, with the increase in age. Ageing decreased the tactile perception of hair. CONCLUSION: Ageing influences the diameter, surface topography, hardness, loss modulus, storage modulus and tactile perception of human hair.

[Role and clinical significance of Th17/Treg balance in patients with severe exacerbation of hepatitis B].

OBJECTIVE: To investigate the role of Th17/Treg balance in immune mechanism in severe exacerbation of hepatitis B. METHODS: The clinical data of 41 patients with chronic hepatitis B were collected, and according to the conditions during hospitalization, these patients were divided into exacerbation group (19 patients) and improvement group (22 patients). On admission, at weeks 1 and 2 of treatment, and at the end of treatment, flow cytometry was used to measure the frequencies of Th17 and Treg cells in peripheral blood, and enzyme-linked immunosorbent assay was used to determine the serum levels of interleukin-17 (IL-17), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß). The dynamic changes in the frequencies of Th17 and Treg cells were compared between the two groups, and the correlation between clinical indices for hepatitis and cytokines was analyzed. The t-test was used for comparison between groups, a one-way analysis of variance was used for comparison within one group across different time points, and Pearson correlation analysis was performed. RESULTS: With disease progression, the exacerbation group showed an increase in the frequency of Th17 cells and a relatively low frequency of Treg cells; compared with the improvement group, the exacerbation group had a higher frequency of Th17 cells and a lower frequency of Treg cells. Th17/Treg ratio gradually increased with exacerbation and decreased with improvement in conditions; in the exacerbation group and the improvement group, Th17/Treg ratio was positively correlated with total bilirubin and negatively correlated with prothrombin activity. In the exacerbation group and the improvement group, Th17 cells were positively correlated with IL-17, and Treg cells were positively correlated with IL-10 and TGF-ß. CONCLUSION: Th17 and Treg cells play important roles in severe exacerbation of hepatitis B, and Th17/Treg ratio may be used as an immunobiological marker for the judgment of severity during severe exacerbation of hepatitis B.