[Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis].

Objective: To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma. Methods: This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect. Results: Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.092, P=0.039),and had a positive predictive effect on the surgical method (ß=0.244,P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions: The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

[Prediction of prognosis of patients with radical resection of intrahepatic cholangiocarcinoma based on single cell omics].

Objectives: To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics. Methods: This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions: The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

[New advances in the diagnosis and treatment of intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer, which has shown an increasing trend in incidence and mortality in recent years, with a poor prognosis. The clinical diagnosis and treatment of ICC currently face the challenges of low detection rate, high mortality rate, poor treatment outcome, and urgently need more in-depth research to promote the improvement of clinical diagnosis and treatment level. In recent years, ICC diagnosis and treatment related research has made new progress in many aspects, and the knowledge about these new clinical diagnosis and treatment advances should be updated in a timely manner. This article reviewed the latest research results in recent years, summarized some new views on ICC typing, prevention and diagnosis staging that have been proposed recently, as well as the new progress made in surgical treatment and systemic treatment, and briefly discussed the potential of ICC individualized precision treatment and the occurrence of rare complications caused by combined treatment.

[A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey].

Objective: To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors. Methods: From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions. Results: Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects (χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients (χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications (χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment (R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not (OR=1.83, P<0.001). Conclusions: Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Synthesis, antiproliferative and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors.

As a target for clinical anti-cancer treatment, epidermal growth factor receptor (EGFR) exhibits its over-expression on various tumour cells and is associated with the development of a variety of human cancers. Herein, we described the synthesis, antiproliferative activity assay and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors. Compared with Gefitinib, some of the target compounds have excellent antiproliferative activities against EGFR-expressed A431 cell line. The robust and reliable 4D-QSAR was constructed using comparative distribution detection algorithm, ordered predictors selection and genetic algorithm method, and the following acceptable statistics are shown: r2 = 0.82, Q2LOO = 0.67, Q2LMO = 0.61, r2Pred = 0.78.

[Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis].

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

The liquid Kangfuxin (KFX) has efficient antifungal activity and can be used in the treatment of vulvovaginal candidiasis in mice.

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.

[PD-1 is associated with CD8(+)T lymphocyte dysfunction in patients with acute and chronic liver failure].

Objective: To explore whether peripheral blood CD8(+)T lymphocyte dysfunction is correlated with the programmed death receptor-1 (PD-1) expression in patients with acute-on-chronic liver failure (HBV-ACLF). Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients with HBV-ACLF and healthy controls. CD8(+)T lymphocytes number and PD-1 expression condition in CD8(+)T lymphocytes were detected by flow cytometry. CD8(+)T lymphocytes isolated from peripheral blood of HBV-ACLF patients were further cultured in vitro. One group was added with PD-L1-IgG fusion protein (ACLF+PD-1 group), and the other group was added with IgG fusion protein (ACLF group). Proliferation ability (ki67), cell viability (CD69), and secretion ability of effector cytokines (IL-2, IFN-γ, TNF-α) were analyzed. Results: 30 cases with HBV-ACLF and healthy controls were enrolled. CD8(+)T lymphocytes absolute number was significantly lower in the peripheral blood of patients with ACLF group (333.88 ± 147.74)/µl than healthy controls (872.50 ± 206.64)/µl (P < 0.001). PD-1 expression in peripheral blood CD8(+)T lymphocytes were significantly increased in ACLF group (13.33% ± 2.52%), (P = 0.027) than healthy controls (7.02% ± 2.12%). In in vitro culture, compared with healthy controls, the peripheral blood CD8(+)T lymphocytes cell viability (CD69), proliferation ability (ki67) (all P ​​< 0.001), and the level of cytokine production (IL-2, IFN-γ, TNF-α) (all P < 0.05) were equally weakened in patients with ACLF group. Compared with ACLF group, CD8(+)T cell viability (CD69), proliferation ability (KI67) (all P < 0.05), and the level of cytokine production were weakened in ACLF+PD-1 group (all P < 0.05). Conclusion: HBV-ACLF patients have CD8(+)T lymphocyte dysfunction. Therefore, PD-1 may have correlation in the regulation of CD8(+)T lymphocyte dysfunction in ACLF patients.

Quality of Split-Mouth Trials in Dentistry: 1998, 2008, and 2018.

The objectives of this study were to assess the reporting quality and methodological quality of split-mouth trials (SMTs) published during the past 2 decades and to determine whether there has been an improvement in their quality over time. We searched the MEDLINE database via PubMed to identify SMTs published in 1998, 2008, and 2018. For each included SMT, we used the CONsolidated Standards Of Reporting Trials (CONSORT) 2010 guideline, CONSORT for within-person trial (WPT) extension, and a new 3-item checklist to assess its trial reporting quality (TRQ), WPT-specific reporting quality (WRQ), and SMT-specific methodological quality (SMQ), respectively. Multivariable generalized linear models were performed to analyze the quality of SMTs over time, adjusting for potential confounding factors. A total of 119 SMTs were included. The mean overall score for the TRQ (score range, 0 to 32), WRQ (0 to 15), and SMQ (0 to 3) was 15.77 (SD 4.51), 6.06 (2.06), and 1.12 (0.70), respectively. The primary outcome was clearly defined in only 28 SMTs (23.5%), and only 27 (22.7%) presented a replicable sample size calculation. Only 45 SMTs (37.8%) provided the rationale for using a split-mouth design. The correlation between body sites was reported in only 5 studies (4.2%) for sample size calculation and 4 studies (3.4%) for statistical results. Only 2 studies (1.7%) performed an appropriate sample size calculation, and 46 (38.7%) chose appropriate statistical methods, both accounting for the correlation among treatment groups and the clustering/multiplicity of measurements within an individual. Results of regression analyses suggested that the TRQ of SMTs improved significantly with time (P < 0.001), while there was no evidence of improvement in WRQ or SMQ. Both the reporting quality and methodological quality of SMTs still have much room for improvement. Concerted efforts are needed to improve the execution and reporting of SMTs.

Prevalence and Risk Factors Governing the Loss of Muscle Function in Elderly Sarcopenia Patients: A longitudinal Study in China with 4 Years of Follow-Up.

OBJECTIVES: Data regarding the occurrence of risk factors that promote the loss of muscle mass, strength and function in sarcopenia patients in elderly Chinese patients are sparse. Here, we investigated the alterations in muscle mass, function and strength in those with sarcopenia over a 4-year period. We further evaluated the risk factors leading to a loss of grip strength, gait speed and skeletal muscle mass index in sarcopenia patients. DESIGN: A face-to-face cross-sectional survey. SETTING AND PARTICIPANTS: The study population consisted of 560 Chinese aged over 59 years. MEASUREMENTS: Study recordings took places over a four-year period from 2014. Muscle mass was assessed through bioelectrical impedance analysis (BIA) performed on an Inbody720, Biospace. Hand-grip strength and 6 m walking speed were used as measurements of muscle strength and function. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria (AWGS). RESULTS: In total, 474 of the elderly residents completed the follow-up. The rates of decreased ASMI, grip strength, and gait speed in the sarcopenia patients increased over the 4-year period. Following multivariate analysis, age was identified as the main risk factor for all the observed decrease, gender was specifically related to the loss of ASMI, stroke was a risk factor for gait speed and sarcopenia. A high BMI was a risk factor for a low gait speed but was protective for a loss of skeletal muscle mass and sarcopenia. CONCLUSIONS: Age leads to a decline in muscle strength and function. In elderly Chinese patients with sarcopenia, the rates of reduced grip strength, gait-speed and sarcopenia increased. A high BMI was protective against the decline in muscle mass and sarcopenia, but represented a risk factor for low gait speed. Stoke was identified to cause a loss of gait speed in sarcopenia patients.

[Advances in the research of smart dressings].

Smart dressings, which show obvious advantage and potential in wound treatment and real-time monitoring, attract widespread attention in recent years. Real-time and dynamic acquiring wound information is vital to the treatment and prognosis of wound. Further research on smart dressings is helpful for wound management, personalized treatment, and realization of medical application translation of health monitoring technology. In the article, we categorize smart dressings and conclude their functions according to the type of micro-environment information of wound gathered by smart dressings.

[Effect of NLRP3 mediated pyroptosis in myocardial cells undergoing hypoxia/deoxygenation injury].

Objective: To investigate the effect of NACHT-LRR-PYD- containing proteins 3 (NLRP3) mediated pyroptosis in myocardial cells undergoing hypoxia/deoxygenation (H/R) injury. Methods: In order to observe whether H/R-treatment could cause pyroptosis, H9c2 cells were divided into 2 groups randomly using the lottery method: control group(without H/R-treatment) and H/R group (in which the H9c2 cells were underwent H/R-treatment). In order to clarify the role of pyroptosis in H/R-injury, H9c2 cells were divided into 4 groups randomly using the lottery method: control group(in which the H9c2 cells were cultivated with normal medium); YVAD group(in which the H9c2 cells were pretreated with z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-YVAD-FMK) 20 µm for 4 hours, then replaced with normal medium); H/R group(H9c2 cells underwent H/R-treatment); YVAD+H/R group (in which the H9c2 cells were pretreated with 20 µm Z-YVAD-FMK for 4 hours before H/R-treatment). To determine whether H/R-induced cell pyroptosis is associated with NLRP3, H9c2 cells were divided into 4 groups randomly using the lottery method: control group (in which cells were transfected with a control nonspecific siRNA); si-NLRP3 group (in which cells were transfected with NLRP3-targeting siRNA); H/R group(in which cells were transfected with a control nonspecific siRNA before H/R-treatment); si-NLRP3+H/R group(in which the H9c2 cells were transfected with NLRP3-targeting siRNA before H/R-treatment). Pore formation on cell membrane was detected by propidium iodide (PI) staining. Cell viability was detected by CCK8 reagent. The protein expression of Caspase-1, interleukin-1ß (IL-1ß) and NLRP3 was detected by Western blot. Results: (1) The positive rate of PI staining ((26.46±5.15)% vs. (1.69±0.73)%,P<0.01), expression of NLRP3 (0.57±0.16 vs. 0.23±0.06,P<0.01), expression of Caspase-1 (1.07±0.13 vs. 0.37±0.08,P<0.01), and expression of IL-1ß (0.38±0.08 vs. 0.16±0.05,P<0.01) were significantly higher in H/R group than in control group. (2)The cell vitality was significantly higher in YVAD+H/R group than in H/R group ((87.31±9.05)% vs. (73.30±7.19)%, P<0.05).The positive rate of PI staining was significantly decreased in YVAD+H/R group than in H/R group ((18.12±4.36)% vs. (26.45±4.60)%, P<0.05). The expression of Caspase-1 (0.72±0.12 vs. 1.07±0.15, P<0.05) and IL-1ß(0.29±0.07 vs. 0.39±0.06, P<0.05) were significantly lower in YVAD+H/R group than in H/R group. (3) The cell vitality was significantly increased in si-NLRP3+H/R group than in H/R group ((85.46±7.71)% vs. (72.41±5.53)%, P<0.05). The positive rate of PI staining was significantly lower in si-NLRP3+H/R group than in H/R group ((18.22±4.20)% vs. (26.73±3.26)%, P<0.05). The expression of Caspase-1(0.87±0.07 vs. 1.15±0.15, P<0.05) and IL-1ß(0.41±0.07 vs. 0.58±0.10, P<0.05) were significantly decreased in si-NLRP3+H/R group than in H/R group. Conclusion: NLRP3 mediated pyroptosis is involved in H/R injury of myocardial cells.

Does audiovisual distraction reduce dental anxiety in children under local anesthesia? A systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis on the effects of audiovisual distraction on reducing dental anxiety in children during dental treatment under local anesthesia. METHODS: The authors identified eligible reports published through August 2017 by searching PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Clinical trials that reported the effects of audiovisual distraction on children's physiological measures, self-reports, and behavior rating scales during dental treatment met the minimum inclusion requirements. The authors extracted data and performed a meta-analysis of appropriate articles. RESULTS: Nine eligible trials were included and qualitatively analyzed; some of these trials were also quantitatively analyzed. Among the physiological measures, heart rate or pulse rate was significantly lower (p = .01) in children subjected to audiovisual distraction during dental treatment under local anesthesia than in those who were not; a significant difference in oxygen saturation was not observed. The majority of the studies using self-reports and behavior rating scales suggested that audiovisual distraction was beneficial in reducing anxiety perception and improving children's cooperation during dental treatment. CONCLUSION: The audiovisual distraction approach effectively reduces dental anxiety among children. Therefore, we suggest the use of audiovisual distraction when children need dental treatment under local anesthesia.

Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori.

Isopentenylation at A37 (i6 A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1-BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock-down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i6 A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.

[Research on the reliability and validity of postural workload assessment method and the relation to work-related musculoskeletal disorders of workers].

OBJECTIVE: To form a new assessment method to evaluate postural workload comprehensively analyzing the dynamic and static postural workload for workers during their work process to analyze the reliability and validity, and to study the relation between workers' postural workload and work-related musculoskeletal disorders (WMSDs). METHODS: In the study, 844 workers from electronic and railway vehicle manufacturing factories were selected as subjects investigated by using the China Musculoskeletal Questionnaire (CMQ) to form the postural workload comprehensive assessment method. The Cronbach's α, cluster analysis and factor analysis were used to assess the reliability and validity of the new assessment method. Non-conditional Logistic regression was used to analyze the relation between workers' postural workload and WMSDs. RESULTS: Reliability of the assessment method for postural workload: internal consistency analysis results showed that Cronbach's α was 0.934 and the results of split-half reliability indicated that Spearman-Brown coefficient was 0.881 and the correlation coefficient between the first part and the second was 0.787. Validity of the assessment method for postural workload: the results of cluster analysis indicated that square Euclidean distance between dynamic and static postural workload assessment in the same part or work posture was the shortest. The results of factor analysis showed that 2 components were extracted and the cumulative percentage of variance achieved 65.604%. The postural workload score of the different occupational workers showed significant difference (P<0.05) by covariance analysis. The results of nonconditional Logistic regression indicated that alcohol intake (OR=2.141, 95%CI 1.337-3.428) and obesity (OR=3.408, 95%CI 1.629-7.130) were risk factors for WMSDs. The risk for WMSDs would rise as workers' postural workload rose (OR=1.035, 95%CI 1.022-1.048). There was significant different risk for WMSDs in the different groups of workers distinguished by work type, gender and age. Female workers exhibited a higher prevalence for WMSDs (OR=2.626, 95%CI 1.414-4.879) and workers between 30-40 years of age (OR=1.909, 95%CI 1.237-2.946) as compared with those under 30. CONCLUSION: This method for comprehensively assessing postural workload is reliable and effective when used in assembling workers, and there is certain relation between the postural workload and WMSDs.

Tear osteopontin level and its relationship with local Th1/Th2/Th17/Treg cytokines in children with allergic conjunctivitis

Background: Allergic conjunctivitis (AC) is one of the most common allergic ocular diseases worldwide. Osteopontin (OPN), as a recently described Th2 inflammation related protein, may play a role in the pathogenesis of AC. The aim of this study was to identify the expression of OPN in children with AC. Methods: Eighty AC children (seasonal and perennial AC) and twenty controls were enrolled in this study. Serum and tears of different time points (during and out of the pollen season) were collected and used for enzyme-linked immunosorbent assay (ELISA) of OPN and T-help cell related cytokines, respectively. The relationship between serum and tears OPN and Th1/2/17Treg related cytokines as well as disease severity were analysed. Results: Our results showed that expression of tear OPN protein by perennial AC patients increased significantly compared with controls or seasonal AC patients out of the pollen season. Tear OPN expression was positively related to local Th2/17 cytokines and negatively related to IL-10 and TGF-Beta expression. The tear OPN expression was also significantly related to disease severity. Conclusion: Tear OPN reflects the local clinical status of ocular allergy and might play an important pathophysiological role in local Th2/17/Treg inflammation in children with AC (AU)

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Interleukin-armed chimeric antigen receptor-modified T cells for cancer immunotherapy.

Chimeric antigen receptor-modified T cells (CAR-T) are endowed with cytotoxic specificity to tumor cells. Although CAR-T-based cancer immunotherapy presents curable therapeutic potential for hematological malignancies, achieving substantial efficacy for solid tumors remain challenging. Researchers have exploited many strategies to enhance the anti-tumor efficacy of CAR-T cells for solid tumors, among which cytokine-armed CAR-T cells improve the proliferation, survival, homing and other properties of CAR-T cells. Interleukins (ILs), pivotal cytokines that affect the function of immune cells, were co-expressed in CAR-T cells or combinatorially administered to enhance the therapeutic potential in clinical trials. In this review, we summarize the strategies exploited by ILs to improve the anti-cancer ability of CAR-T cells and the different impacts of different ILs on CAR-T cells.