[Analysis of changes in reporting and diagnosis of pulmonary tuberculosis among children in Liangshan Yi Autonomous Prefecture, Sichuan Province from 2019 to 2021].

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.

[Investigation and influencing factors on pelvic floor muscle strength of 929 adult females in gynecological outpatient department].

Objective: To investigate the present situation of pelvic floor muscle strength, and to analyze the factors affecting pelvic floor muscle strength. Methods: The data of patients who were admitted into the general outpatient department of gynecology, Peking University People's Hospital from October 2021 to April 2022 were collected, and the patients who met the exclusion criteria were included in this cross sectional study. The patient's age, height, weight, education level, defecation way and defecation time, birth history, maximum newborn birth weight, occupational physical activity, sedentary time, menopause, family history and disease history were recorded by questionnaire. Morphological indexes such as waist circumference, abdomen circumference and hip circumference were measured with tape measure. Handgrip strength level was measured with grip strength instrument. After performing routine gynecological examinations, the pelvic floor muscle strength was evaluated by palpation with modified Oxford grading scale (MOS). MOS grade>3 was taken as normal group and ≤3 as decreased group. Binary logistic regression was used to investigate the related factors of deceased pelvic floor muscle strength. Results: A total of 929 patients were included in the study, and the average MOS grade was 2.8±1.2. By univariate analysis, birth history, menopausal time, defecation time, handgrip strength level, waist circumference and abdominal circumference were related to the decrease of pelvic floor muscle strength (all P<0.05). By binary logistic regression analysis, the level of handgrip strength (OR=0.913, 95%CI: 0.883-0.945; P<0.001) was correlated with normal pelvic floor muscle strength; waist circumference (OR=1.025, 95%CI: 1.005-1.046; P=0.016), birth history (OR=2.224, 95%CI: 1.570-3.149; P<0.001), sedentary time> 8 hours (OR=2.073, 95%CI: 1.198-3.587; P=0.009) were associated with the decrease of pelvic floor muscle strength. Conclusions: The level of handgrip strength is related to the normal pelvic floor muscle strength of females, while the waist circumference, birth history and sedentary time>8 hours are related to the decrease of pelvic floor muscle strength of females. In order to prevent the decrease of pelvic floor muscle strength, it is necessary to carry out relevant health education, enhance exercise, improve the overall strength level, reduce daily sedentary time, maintain symmetry, and carry out comprehensive overall intervention to improve pelvic floor muscle function.

[Changes in percentage of GATA3+ regulatory T cells and their pathogenic roles in allergic rhinitis].

OBJECTIVE: To investigate the changes in percentage of GATA3+ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models. METHODS: The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines. RESULTS: Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3+ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05). CONCLUSION: The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3+ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3+ Treg cells as a new therapeutic target for AR.

MiR-139 Affects Radioresistance in Esophageal Cancer by Targeting the PDK1/AKT/Cyclin D1 Signaling Pathway.

We explored the mechanism by which miR-139 modulates radioresistance of esophageal cancer (EC). The radioresistant cell line KYSE150R was obtained from the parental KYSE150 cell line by fractionated irradiation (15×2 Gy; total dose of 30 Gy). The cell cycle was assessed by flow cytometry. A gene profiling study was conducted to detect the expression of genes related to the radioresistance of EC. In the KYSE150R line, flow cytometry revealed increased number of G1-phase cells and decreased number of G2-phase cells; the expression of miR-139 increased. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. Western blotting showed that miR-139 knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. However, PDK1 inhibitor GSK2334470 reversed this effect for p-AKT and cyclin D1 expression. A luciferase reporter assay indicated that miR-139 directly bound to the PDK1 mRNA 3'-UTR. Analysis of the clinical data from 110 patients with EC showed an association of miR-139 expression with the TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival. In conclusion, miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.

[Problems to be solved in the development from the perspective of future application scenarios of telesurgery].

Telemedicine, which integrates medicine, communication, engineering, information and other disciplines, is a hot emerging cross field in recent years. With the development of telecommunication technology and surgical robot, telesurgery is regarded as the "crown pearl" in telemedicine and has attracted more and more attention. As an extension of traditional surgery, telesurgery greatly extends the connotation and concept of surgery and embodies the great leap forward development of surgical technology. Despite the current limitations such as network delay, transparency of remote robot operation and team construction of surgeons, telesurgery has still formed a variety of innovative application scenarios and achieved rapid development in China in recent years. In view of the uneven distribution of medical resources in China and the epidemic of COVID-19 in the world, this paper puts forward the possible problems and solutions in the development of telesurgery, and looks forward to the feasibility of telesurgery technology in process of shifting the focus of medical and health care down to the community level, channeling resources accordingly.

Surprisingly good thermoelectric performance of monolayer C3N.

The rapid emergence of graphene has attracted numerous efforts to explore other two-dimensional materials. Here, we combine first-principles calculations and Boltzmann theory to investigate the structural, electronic, and thermoelectric transport properties of monolayer C3N, which exhibits a honeycomb structure very similar to graphene. It is found that the system is both dynamically and thermally stable even at high temperature. Unlike graphene, the monolayer has an indirect band gap of 0.38 eV and much lower lattice thermal conductivity. Moreover, the system exhibits obviously larger electrical conductivity and Seebeck coefficients for the hole carriers. Consequently, theZTvalue ofp-type C3N can reach 1.4 at 1200 K when a constant relaxation time is predicted by the simple deformation potential theory. However, such a largerZTis reduced to 0.6 if we fully consider the electron-phonon coupling. Even so, the thermoelectric performance of monolayer C3N is still significantly enhanced compared with that of graphene, and is surprisingly good for low-dimensional thermoelectric materials consisting of very light elements.

A diagnostic test that uses isothermal amplification and lateral flow detection sdaA can detect tuberculosis in 60 min.

AIMS: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is now the leading cause of death from infectious disease, thus rapid diagnostic and screening techniques for TB are urgently needed. METHODS AND RESULTS: Here, a detection of MTB using multiple cross displacement amplification coupling with nanoparticles-based lateral flow device (MCDA-LFD) was developed and validated, targeting the specific sdaA gene. The whole detection procedure, including rapid genomic DNA extraction (15 min), amplification (30 min) and result reporting (2 min), was completed within 50 min. No cross-reaction with non-mycobacteria and non-tuberculous mycobacteria (NTM) strains was observed. The sensitivity of sdaA-MCDA-LFD, Xpert MTB/RIF assay and culture results was 81·6, 48·3 and 37·9%, respectively, in TB patients. Among positive culture samples, the sensitivity of sdaA-MCDA-LFD and Xpert MTB/RIF assay was 93·9% (31/33) and 81·8% (27/33), respectively. Among culture-negative samples, the sensitivity of sdaA-MCDA-LFD and Xpert MTB/RIF assay was 74·1% (40/54) and 27·8% (15/54), respectively. The specificity of sdaA-MCDA-LFD and Xpert MTB/RIF was 95·4% (62/65) and 100% (65/65) in clinical samples from non-TB patients. CONCLUSION: The sdaA-MCDA-LFD assay was a rapid, simple, specific and sensitive TB diagnostic test. SIGNIFICANCE AND IMPACT OF THE STUDY: The sdaA-MCDA-LFD assay holds promise for application as a useful point-of-care test to detect MTB, and will play an important role in controlling and preventing TB.

MiRNA-409-5p dysregulation promotes imatinib resistance and disease progression in children with chronic myeloid leukemia.

OBJECTIVE: To elucidate the role of miRNA-409-5p in the pathogenesis of child chronic myeloid leukemia (CML) and its potential mechanism. PATIENTS AND METHODS: Expression levels of miRNA-409-5p and NUP43 in peripheral blood of CML children and healthy controls were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and flow cytometry were conducted to evaluate the regulatory effect of miRNA-409-5p on proliferative potential and cell cycle progression of CML cells. Protein levels of PCNA, c-Myc, and cyclin D1 in CML were examined by Western blot. Dual-luciferase reporter gene assay verified the binding of target gene NUP43 to miRNA-409-5p. Finally, the potential effect of miRNA-409-5p on Imatinib resistance in CML was elucidated. RESULTS: Compared with healthy children, miRNA-409-5p expression in peripheral blood of CML children markedly decreased. Similarly, miRNA-409-5p expression was lower in CML cells. Contrary to the expression pattern of miRNA-409-5p, NUP43 was highly expressed in CML. The miRNA-409-5p overexpression remarkably inhibited proliferative potential and arrested cell cycle in the G0/G1 phase. Protein levels of PCNA, c-Myc, and cyclin D1 were downregulated in CML cells overexpressing miRNA-409-5p. The knockdown of miRNA-409-5p obtained the opposite trends. NUP43 was proved to be the target gene of miRNA-409-5p and negatively regulated by miRNA-409-5p. After overexpression of miRNA-409-5p, Imatinib treatment elevated proliferation inhibition and cell cycle arrest of K562 and KG-1a cells. CONCLUSIONS: MiRNA-409-5p is lowly expressed in child CML, which inhibits proliferative potential and cell cycle progression by upregulating NUP43 expression. In addition, miRNA-409-5p overexpression enhances Imatinib resistance in CML.

[Expression and significance of Notch1-Jagged1 in allergic rhinitis].

Objective: To study the expression and significance of Notch1-Jagged1 in nasal mucosa of allergic rhinitis (AR) mouse model in various stages and in the serum of AR patients. Methods: Thirty-six mice were divided into 3 groups: control group, basal sensitization group (OVA) and OVA/AR group, with 12 mice in each group. Allergic symptom in each group were scored after AR model establishment. HE staining method was used to observe the nasal mucosa eosinophils infiltration. ELISA was used to detect the serum level of total IgE. Flow cytometry was used to detect the change of Treg cells in each group. Western blot was used to detect the expression of Notch1 and Jagged1 in nasal mucosa. Flow cytometric bead array (CBA) was used to detect the level of Th1/Th2/Th17 cytokines in splenic lymphocytes. The serum was obtained from 50 patients with AR and 30 control volunteers in Department of Otorhinolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University from June to October 2017. ELISA was used to detect the expression of Notch1 and Jagged1. Results: Compared with the control group, the allergy symptom, the number of nasal mucosal eosinophils and the level of total IgE were not significantly different in basal sensitization group, but increased significantly in OVA/AR group (6.11±0.78 vs 0.67±0.50, 77.67±5.61 vs 10.33±0.82, (106.80±11.91) pg/ml vs (82.45±19.80) pg/ml, t value was 19.471, 34.848, 2.542, respectively, all P<0.05). Compared with the control group, the ratio of Treg cell increased in basal sensitization group but decreased in OVA/AR group ((10.29±0.47)% vs (9.28±0.16)%, (8.49±0.15)% vs (9.28±0.16)%, t value was 5.838, 4.540, respectively, all P<0.01). Compared with control group, the expression of Notch1 increased significantly both in basal sensitization group and OVA/AR group (1.04±0.05 vs 0.71±0.05, 1.83±0.10 vs 0.71±0.05, t value was 9.293, 31.363, respectively, all P<0.01); and the expression of Jagged1 only increased significantly in OVA/AR group (0.41±0.04 vs 0.21±0.01, t=13.472, P<0.01). It was found that Notch1 was positively correlated with the level of IL-6, IL-10 by Pearson test (r value was 0.98, 0.87, respectively, all P<0.01). Compared with control volunteers, the expression of Notch1 and Jagged1 increased significantly in AR group patients ((1 135.0±254.9) pg/ml vs (436.0±139.3) pg/ml, (1 200.2±401.0) pg/ml vs (559.9±124.2) pg/ml, t value was 13.99, 11.94, respectively, all P<0.01). Conclusions: The expression of Notch1 receptor and ligand increased significantly in the pathogenesis of AR. Notch1-Jagged1 may promote the occurrence and development of AR by up-regulating the expression of IL-6 and IL-10.

[The roles of IL-17 and CXCR4 in chronic allograft nephropathy in rat models].

Objective: To investigate the role and mechanism of IL-17 and CXCR4 in chronic graft nephropathy (CAN) in rat models. Methods: CAN rat models were established using Fisher 344 to Lewis rats. In the control group(n=10), Lewis rats were performed isotransplantation. CAN rat models were established in experimental group(n=10). All the rats were havested 6 weeks after transplantation. Kidneys were examined by pathology to evaluate the injury of the renal allograft. SDF-1/CXCR4, IL-17 and α-SMA expression level in serum and renal graft were detected by immunohistochemical staining and Enzyme-linked immunosorbent assays(ELISA). The percent and the absolute amount of CD4(+) cells、CXCR4(+) cells and IL-17(+) cells were detected by flow cytometry. Results: The graft of the experiment group showed obvious pathological features of CAN. The protein expression levels of SDF-1/CXCR4 and IL-17 in the experiment group are significantly higher than in the control group. We could also observe the number of Th17 cells has a significant increase in the experiment group[blood (0.19±0.05)% vs (0.12±0.03)%; kidney (0.52±0.21)% vs (0.17±0.12)%]. The IL-17 level also showed the same differences between the experiment[blood (243.12±17.63) pg/ml, kidney (521.54±21.76) pg/ml]and the control group[blood (35.78±7.3) pg/ml, kidney (77.34±11.1) pg/ml]. Conclusions: The Th17 cells increase in the CAN rats model, maybe the SDF-1/CXCR4 has a chemotaxis to collect Th17 cells to the injured kidney. And its expression of IL-17 may promote the renal cells to transform into fibroblasts.

Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice.

The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with high-dose tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue, and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides, and Lactobacillus and CD4+ CD25hi FoxP3+ regulatory T cells in the colonic mucosa and the circulation. These were significantly increased after either tacrolimus treatment or treatment by fecal microbiota transfer from tacrolimus-treated donors. Further, treatment with low-dose tacrolimus plus fecal microbiota transfer from high-dose tacrolimus-altered mice increased skin allograft survival rate in a skin transplantation model. Thus, high-dose tacrolimus alters the compositions and taxa of the gut microbiota. Administration of these conditioned gut microbiota plus low-dose tacrolimus resulted in regulation of colonic and systemic immune responses and an increased allograft survival rate. This study demonstrated a new strategy for controlling allograft rejection by combining an immunosuppressive agent with gut microbiome transplantation.

Evidence of s-wave superconductivity in the noncentrosymmetric La7Ir3.

Superconductivity in noncentrosymmetric compounds has attracted sustained interest in the last decades. Here we present a detailed study on the transport, thermodynamic properties and the band structure of the noncentrosymmetric superconductor La 7 Ir 3 (T c ~ 2.3 K) that was recently proposed to break the time-reversal symmetry. It is found that La7Ir3 displays a moderately large electronic heat capacity (Sommerfeld coefficient γ n ~ 53.1 mJ/mol K2) and a significantly enhanced Kadowaki-Woods ratio (KWR ~32 µΩ cm mol2 K2 J-2) that is greater than the typical value (~10 µΩ cm mol2 K2 J-2) for strongly correlated electron systems. The upper critical field Hc2 was seen to be nicely described by the single-band Werthamer-Helfand-Hohenberg model down to very low temperatures. The hydrostatic pressure effects on the superconductivity were also investigated. The heat capacity below T c reveals a dominant s-wave gap with the magnitude close to the BCS value. The first-principles calculations yield the electron-phonon coupling constant λ = 0.81 and the logarithmically averaged frequency ω ln = 78.5 K, resulting in a theoretical T c = 2.5 K, close to the experimental value. Our calculations suggest that the enhanced electronic heat capacity is more likely due to electron-phonon coupling, rather than the electron-electron correlation effects. Collectively, these results place severe constraints on any theory of exotic superconductivity in this system.

Genotype frequencies of human neutrophil antigen-3 in the Chinese Zhuang and Dong populations.

Individuals with the human neutrophil antigen (HNA)-3b/3b type can produce HNA-3a antibodies, which have been reported to cause severe, sometimes fatal transfusion-related acute lung injury (TRALI). Our study aimed to determine the genotype frequency of HNA-3a/3b which will be helpful to estimate the potential risk for forming anti-HNA-3a, the clinically relevant antibody linked to TRALI in two different ethnic groups of southern China. Five hundred unrelated and healthy blood donors (284 male, 216 female; 300 Zhuangs, 200 Dongs) from the Guangxi Zhuang Autonomous Region were simultaneously typed for the HNA-3 allele using a polymerase chain reaction sequence-based typing (PCR-SBT) method. Genotype frequencies of HNA-3a/3a, HNA-3a/3b and HNA-3b/3b were 51.7%, 39.7% and 8.6% in the Zhuang population, and 44.0%, 49.0% and 7.0% in the Dong population, respectively. Homozygous HNA-3b/3b genotype frequency among the Zhuang population (8.6%) was significantly higher than previously reported in African Americans (0.4%), Brazilians (3.6%) and English Caucasians (2.9%) (p < .05). And the HNA-3b/3b genotype frequency among the Dong population was higher than African Americans (0.4%) (p < .05). This study showed Chinese Zhuang and Dong populations possessed a higher frequency of HNA-3b/3b genotype, suggesting that they may be at greater risk for developing anti-HNA-3a alloantibodies that may cause severe cases of TRALI. A molecular-based identification of the HNA-3b/3b genotype in all multiparous female blood donors was suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusions.

[Factors affecting the participation rates in epidemiologic surveys].

Objective: The aim of this study was to investigate the response in health-related epidemiological investigation among Chinese population aged 15 and over. We analyzed the specific causes of non-response, and explored the effective ways to improve the response rate, so as to provide reference for future epidemiological studies of this kind. Methods: Two modes of studies regarding the prevalence of important cardiovascular diseases were used in Chongqing, during the 12(th) Five-Year Plan period in oder to find out the cause related to non-response. Intervention programs were carried out to evaluate the effects. Results: When using the concentrated mode (CM), the completion rate to the questionnaires was only 20.00% in the pre-investigation, with the response rate as 13.48%. In the deconcentrated mode (DM), the completion rate was 31.16%, with the response rate as 25.19%. After a series of incentives provided to both the respondents and the project-related core staff in the two modes, response rates of the two modes increased to the expected 60%. Conclusions: CM appeared having advantages on quality control, but was more time consuming, with higher cost, and without effective follow-up measures to improve the response rate. However, DM had the advantages on controlling the cost and could increase the response rate through making advanced appointment with the households but quality control remained difficult. Two key points should be strengthened to improve the response rates, which including: Precisely finding out the research objects and providing incentives to the respondents to attract their interests of participating in the investigation.

Identification and characterization of Laodelphax striatellus (Insecta: Hemiptera: Delphacidae) neutral sphingomyelinase.

The neutral sphingomyelinase (nSMase) 1 homologue gene LsSMase was cloned from Laodelphax striatellus, a direct sap-sucker and virus vector of gramineous plants, and expressed via a Bac to Bac baculovirus expression system. The LsSMase-enhanced green fluorescent protein fusion protein was located in the endoplasmic reticulum in a similar manner to mammalian nSMase 1. The biochemical properties of LsSMase were determined in detail. The optimal pH and temperature for recombinant LsSMase were 8 and 37 °C, respectively. LsSMase was an Mg2+ or Mn2+ dependent enzyme, but different concentration of each were needed. The activity of LsSMase was significantly stimulated by Ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EGTA), whereas it was inhibited by ethylenediaminetetraacetic acid. Millimolar concentrations of Zn2+ completely inhibited LsSMase. The reducing agents dithiothreitol and ß-mercaptoethanol varied in their effects on activity. Phospholipids were not found to stimulate LsSMase.

Crystal structure of a bicupin protein HutD involved in histidine utilization in Pseudomonas.

Cupins form one of the most functionally diverse superfamilies of proteins, with members performing a wide range of catalytic, non-catalytic, and regulatory functions. HutD is a predicted bicupin protein that is involved in histidine utilization (Hut) in Pseudomonas species. Previous genetic analyses have suggested that it limits the upper level of Hut pathway expression, but its mechanism of action is unknown. Here, we have determined the structure of PfluHutD at 1.74 Å resolution in several crystallization conditions, and identified N-formyl-l-glutamate (FG, a Hut pathway intermediate) as a potential ligand in vivo. Proteins 2017; 85:1580-1588. © 2017 Wiley Periodicals, Inc.