All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity.

Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience. Our investigation on disinhibitory mechanisms in the classical model of ocular dominance plasticity uncovered an unexpected form of experience-dependent circuit plasticity. In the layer 2/3 of mouse visual cortex, monocular deprivation triggers a complete, "all-or-none," elimination of connections from pyramidal cells onto nearby parvalbumin-positive interneurons (Pyr→PV). This binary form of circuit plasticity is unique, as it is transient, local, and discrete. It lasts only 1 d, and it does not manifest as widespread changes in synaptic strength; rather, only about half of local connections are lost, and the remaining ones are not affected in strength. Mechanistically, the deprivation-induced loss of Pyr→PV is contingent on a reduction of the protein neuropentraxin2. Functionally, the loss of Pyr→PV is absolutely necessary for ocular dominance plasticity, a canonical model of deprivation-induced model of cortical remodeling. We surmise, therefore, that this all-or-none loss of local Pyr→PV circuitry gates experience-dependent cortical plasticity.

The incidence, prevalence, and survival analysis of pancreatic neuroendocrine tumors in the United States.

PURPOSE: The incidence of pancreatic neuroendocrine tumors (pNETs) was increasing. The main purpose of this study was to statistically analyze the incidence and prevalence of pNETs and the main risk factors for the prognosis. METHODS: Based on the Surveillance, Epidemiology, and End Results (SEER) database, with three registries integrated, this study comprehensively displayed the annual age adjust incidence of pNETs from 1975 to 2018, the estimated 20-year limited-duration prevalence, and conducted the univariate and multivariate survival analysis. RESULTS: The incidence of pNETs has increased to about 1.5 per 100,000 population, and the prevalence has reached about 0.008% with the aged, Grade 1 and nonfunctional tumors accounting for the majority. The average median overall survival (OS), 5-year survival rate, and median disease-free survival (DFS) of pNETs patients from 1975 to 2018 were 85 months, 57.55%, and 220 months, respectively. From 2000 to 2018, the median OS was 94 months, and the 5-year survival rate was 59.94%. In multivariate survival analysis, the greatest risk factor was Grade 3&4 with HR = 3.62 (3.10-4.28), followed by distant stage with HR = 2.77 (2.28-3.36), and aged over 80 years old with HR = 2.26 (1.33-3.83). Surgery was a protective prognostic factor with HR = 0.34 (0.29-0.40). CONCLUSION: The incidence and prevalence of pNETs were still increasing, but the trend was gradual and aging in recent years. The survival time of pNETs was longer but has not changed much in recent years. The degrees of malignancy, stage, and operation were the most important prognosis factors.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

[Annual review of interventional pulmonology in 2022].

Interventional pulmonology is an essential part of the treatment of respiratory diseases and an important component of modern respiratory medicine. In recent years, interventional respiratory medicine has kept up with the trend of the times, constantly developing and integrating various techniques, expanding the scope of application of interventional respiratory medicine, and developing in the direction of personalized and precision medicine as well. Here, we reviewed the new progress and up-to-date research achievements of interventional pulmonology from December 2021 to September 2022.

Serine 319 phosphorylation is necessary and sufficient to induce a Cx37 conformation that leads to arrested cell cycling.

Connexin 37 (Cx37; protein product of GJA4) expression profoundly suppresses proliferation of rat insulinoma (Rin) cells in a manner dependent on gap junction channel (GJCh) functionality and the presence and phosphorylation status of its C-terminus (CT). In Rin cells, growth is arrested upon induced Cx37 expression and serine 319 (S319) is frequently phosphorylated. Here, we show that preventing phosphorylation at this site (alanine substitution; S319A) relieved Cx37 of its growth-suppressive effect whereas mimicking phosphorylation at this site (aspartate substitution; S319D) enhanced the growth-suppressive properties of Cx37. Like wild-type Cx37 (Cx37-WT), Cx37-S319D GJChs and hemichannels (HChs) preferred the closed state, rarely opening fully, and gated slowly. In contrast, Cx37-S319A channels preferred open states, opened fully and gated rapidly. These data indicate that phosphorylation-dependent conformational differences in Cx37 protein and channel function underlie Cx37-induced growth arrest versus growth-permissive phenotypes. That the closed state of Cx37-WT and Cx37-S319D GJChs and HChs favors growth arrest suggests that rather than specific permeants mediating cell cycle arrest, the closed conformation instead supports interaction of Cx37 with growth regulatory proteins that result in growth arrest.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies].

To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.

[Analysis of the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 for intrahepatic parenchymal substantial lesions ≤3.0 cm].

Objective: To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm. Methods: A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results: The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively. Conclusions: LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

Comparing transcriptional responses to Fusarium crown rot in wheat and barley identified an important relationship between disease resistance and drought tolerance.

BACKGROUND: Fusarium crown rot (FCR) is a chronic disease in cereal production worldwide. The impact of this disease is highly environmentally dependant and significant yield losses occur mainly in drought-affected crops. RESULTS: In the study reported here, we evaluated possible relationships between genes conferring FCR resistance and drought tolerance using two approaches. The first approach studied FCR induced differentially expressed genes (DEGs) targeting two barley and one wheat loci against a panel of genes curated from the literature based on known functions in drought tolerance. Of the 149 curated genes, 61.0% were responsive to FCR infection across the three loci. The second approach was a comparison of the global DEGs induced by FCR infection with the global transcriptomic responses under drought in wheat. This analysis found that approximately 48.0% of the DEGs detected one week following drought treatment and 74.4% of the DEGs detected three weeks following drought treatment were also differentially expressed between the susceptible and resistant isolines under FCR infection at one or more timepoints. As for the results from the first approach, the vast majority of common DEGs were downregulated under drought and expressed more highly in the resistant isoline than the sensitive isoline under FCR infection. CONCLUSIONS: Results from this study suggest that the resistant isoline in wheat was experiencing less drought stress, which could contribute to the stronger defence response than the sensitive isoline. However, most of the genes induced by drought stress in barley were more highly expressed in the susceptible isolines than the resistant isolines under infection, indicating that genes conferring drought tolerance and FCR resistance may interact differently between these two crop species. Nevertheless, the strong relationship between FCR resistance and drought responsiveness provides further evidence indicating the possibility to enhance FCR resistance by manipulating genes conferring drought tolerance.

[Effect of total prostate volume and transitional zone volume on the curative effect of transurethral resection of prostate in benign prostatic hyperplasia].

Objective: To compare the clinical effect of different total prostate volume (TPV) and different transitional zone volume (TZV) on benign prostatic hyperplasia (BPH) treated with transurethral resection of prostate(TURP). Methods: Clinical data of 210 patients with BPH admitted to Guizhou provincial people's hospital from June 2016 to August 2018 were retrospectively collected and analyzed. All patients underwent transrectal ultrasonography, and they were divided into three groups according to TPV: 70 patients in group A:TPV<40mL, 98 patients in group B: 40 ml≤TPV<80 ml, and 42 patients in group C:TPV≥80 ml. Meanwhile, three groups were divided according to TZV: 88 patients in group a: TZV<20ml, 67 patients in group b: 20 ml≤TZV<40 ml, and 55 patients in group c:TZV≥40 ml. All of the patients with TURP were followed up for 6 months after surgery, and the data of international prostate symptom score (IPSS), storage symptoms IPSS (IPSS-S), voiding symptoms IPSS (IPSS-V), Quality of Life (QoL) index, and maximum urinary flow rate (Qmax) were collected before and after surgery. Finally, the effect of TPV and TZV on TURP was analyzed respectively by analysis of variance. Results: There were no statistically significant differences in preoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax among the three groups of patients grouped by TPV (P>0.05), but the age of patients in group C(73.5±6.5) was significantly higher than that in group A (69.3±7.6) and group B (70.9±7.3) (P=0.015). Postoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax of patients in groups A, B and C also showed no significant difference (P>0.05). There were no statistically significant differences in preoperative IPSS, IPSS-V, IPSS-S, QoL, and Qmax among the three groups of patients grouped according to TZV (P>0.05), while the age of patients in group a (69.2±7.6) was significantly lower than that of patients in group b (72.1±7.2) and group c (72.5±6.7) (P=0.017). There were statistically significant differences in IPSS (P=0.010), IPSS-V (P=0.037), IPSS-S (P=0.022), QoL (P=0.038) and Qmax (P=0.037) among the groups a, b, and c after surgery. Moreover, IPSS, IPSS-V, IPSS-S and QoL were negatively correlated with TZV, while Qmax was positively correlated with TZV. Postoperative IPSS, IPSS-V, IPSS-S, QoL and Qmax were significantly different from those before surgery in groups A, B, C and groups a, b, c (P<0.001). Conclusion: TPV and TZV may not be significantly correlated with BPH symptoms, but may be correlated with age. TURP is an effective treatment for patients with different TPV and TZV. There is no significant statistical difference in the surgical efficacy among patients with different TPV, but patients with larger TZV tended to have better outcome. TZV may be better than TPV in predicting the postoperative efficacy.

[The mechanism of circ_0023990/miR-873-5p/ANXA2 axis regulating radiosensitivity and development of thyroid carcinoma].

Objective: To explore the effect and possible mechanism of circ_0023990 on the radiosensitivity of thyroid cancer cells. Methods: qRT-PCR was used to detect the expression of circ_0023990 in the cancer tissues of 55 patients with thyroid cancer and thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62), and the relationship between the expression of circ_0023990 in cancer tissues and the clinical characteristics of the patients were analyzed. Thyroid cancer cells TPC-1 and KTC-1 were divided into sh-circ_0023990 group, sh-NC group, sh-circ_0023990+anti-miR-873-5p group, sh-circ_0023990+anti-miR-NC group, miR-873-5p group, miR-NC group, miR-873-5p+pcDNA-ANXA2 group and miR-873-5p+pcDNA group, and then clone formation experiment was used to detect cell radiosensitivity. After each group of cells was irradiated with 4Gy radiation, the expression of γH2AX protein in the cells was detected by Western Blot. The dual luciferase reporter gene experiment verified the targeting relationship between circ_0023990 and miR-873-5p or miR-873-5p and ANXA2. Results: The expression of circ_0023990 in thyroid cancer tissues was higher than that in normal tissues (2.15±0.09 vs. 0.97±0.05, P<0.05), and its expression was closely related to tumor size, lymph node metastasis and TNM staging of patients with thyroid cancer (P<0.05). The expression of circ_0023990 in thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62) were higher than that of normal thyroid cells HTori-3 (3.16±0.38, 2.63±0.28, 1.82±0.24, 1.71±0.22 vs. 1.00±0.10, all P<0.05). The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990 group were significantly lower than those in the sh-NC group (P<0.05), and the sensitization ratios were 2.482, 1.643; The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990+anti-miR-873-5p group were higher than those in the sh-circ_0023990+anti-miR-NC group (P<0.05), and the sensitization ratios were 0.305, 0.441, respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p group were lower than those in the miR-NC group (P<0.05), and the sensitization ratios were 2.044, 1.653 respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p+pcDNA-ANXA2 group was higher than that in the miR-873-5p+pcDNA group (P<0.05), and the sensitization ratios were 0.496, 0.686, respectively. The expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990 group were higher than that in the 4 Gy+sh-NC group (2.68±0.27 vs. 1.87±0.25, 2.46±0.19 vs. 1.77±0.14; all P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990+anti-miR-873-5p group were lower than that in the 4 Gy+sh-circ_0023990+anti-miR-NC group (1.13±0.09 vs. 1.69±0.09, 1.11±0.08 vs. 1.60±0.08; both P<0.05). The expression of γH2AX protein in TPC-1 and KTC-1 cells in the 4 Gy+miR-873-5p group were higher than that in the 4 Gy+miR-NC group (2.35±0.16 vs. 1.84±0.14, 2.26±0.12 vs. 1.77±0.13; both P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+miR-873-5p+pcDNA-ANXA2 group were lower than that in the 4 Gy+miR-873-5p+pcDNA group (1.96±0.12 vs. 2.41±0.12, 1.92±0.07 vs. 2.28±0.12; both P<0.05). circ_0023990 targeted the negative regulation of miR-873-5p, and ANXA2 was the target gene of miR-873-5p. Conclusion: circ_0023990 was highly expressed in thyroid cancer tissues and cell lines, and it may promote the radiotherapy resistance of thyroid cancer cells in vivo through regulating miR-873-5p/ANXA2 axis.

[Value of IgA antiphospholipid antibodies in diagnosis of the antiphospholipid syndrome].

Objective: To examine the prevalence of multiple antiphospholipid antibodies (aPL) subtypes in healthy people and antiphospholipid syndrome (APS) patients, and to assess the value of IgA-aPL in the diagnosis of APS. Methods: According to the 2006 Sydney International APS Classification Criteria, a total of 218 APS patients who were admitted to Peking Union Medical College Hospital or West China Hospital of Sichuan University from July to December 2019 were enrolled. Among them, 66 were males, and 152 were females, aged (44.5±15.4) years, including 148 primary APS patients and 70 secondary APS patients. Age-and gender-matched controls were collected at the same period at the ratio of 1∶1 with the APS cases. IgA/IgG/IgM anticardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI) were detected by chemiluminescent immunoassay. The differences of indicators between groups were analyzed, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of IgA-aPL for APS. Results: The positivity of IgA-aCL and IgA-aß2GPI was 20.6% and 15.6% in the APS patients, while in the IgG/IgM-aCL or IgG/IgM-aß2GPI negative individuals, the isolated positivity of IgA-aCL and IgA-aß2GPI was only 2.3% and 0.9%, respectively. Accordingly, IgA-aCL and IgA-aß2GPI isolated positivity could be used to diagnose APS (P=0.216, 1, respectively). The area under the ROC curve (AUC) of IgG/IgM-aCL for APS diagnosis was 0.833, which was significantly better than that of IgG-aCL alone (AUC=0.776, P<0.001); while the AUC of IgA/IgG/IgM-aCL was 0.833, which could not further increase the diagnostic value for APS (P=0.287). As for aß2GPI, the diagnostic efficacy of combined IgG/IgM (AUC=0.875) or IgA/IgG/IgM (AUC=0.875) antibodies was not superior to IgG-aß2GPI used alone (AUC=0.869, both P>0.05). Besides, patients with IgA-aPL were more likely to have heart valve lesions and thrombocytopenia (both P<0.05). Conclusion: Based on the existing serological markers, such as lupus anticoagulant, IgG/IgM subtype of aCL and aß2GPI, testing IgA-aCL and IgA-aß2GPI cannot further improve the predictive value of APS. However, IgA-aPL is associated with clinical manifestations of APS, including heart valve lesions and thrombocytopenia.

[Comparison of trends in congenital heart disease mortality from 1990 to 2017 between China and North America].

Objective: To compare trends in congenital heart disease (CHD) mortality between China and North America from 1990 to 2017. Methods: Using the data from the Global Burden Of Disease (GBD) study 2017, we analyzed the related indicators of CHD mortality in China and North America from 1990 to 2017, including standardized mortality, number of deaths, age distribution of death population and age-specific mortality of CHD in each birth cohort. Age-period-cohort model was used to calculate the annual percent change of age-standardized and age-specific mortality rates of CHD (% per year), period effect-adjusted age-specific mortality rates, and the relative risk of death among CHD population at different time periods (2000－2004 as reference period) and different birth cohorts (1970 as reference cohort). Results: In 2017, the age-standardized mortality rates for CHD in China and North America were 2.63/100 000 and 1.13/100 000 respectively, a decrease of 50.4% and 49.4% compared to 1990. Of all deaths from CHD in China, 76.8% were found in children under 5 years, which was higher than that in North America (51.7%). For population under 40 years, the period effect-adjusted age-specific mortality was higher in China (0.46-167.94 per 100 000 person-years) than in North America (0.68-22.47 per 100 000 person-years); whereas for population over 40 years, mortality was lower in China (0.13-0.34/100 000 person years) than in North America (0.43-0.72/100 000 person-years).From 1990 to 2017, CHD mortality in China decreased by 1.95% per year. The annual decrease of mortality ranged from 1.95% to 3.64% per year in population under 45 years, but the mortality showed increasing trends among those over 50 years. In 2015－2019, the relative risk of death from CHD decreased by 31% in China and 24% in North America. For 2015 birth cohort, the relative risk of death decreased by 84% in China and by 64% in North America. Conclusions: In the past 30 years, the risk of death from CHD in China has significantly decreased, and the survival gap with North America is dramatically narrowed. However, mortality is higher among younger populations in China than in North America, and the mortality in the elders shows increasing trends each year in China.

Hypoxia-responsive miR-346 promotes proliferation, migration, and invasion of renal cell carcinoma cells via targeting NDRG2.

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. In this study, we investigated the role of miR-346 in RCC cells under hypoxia. OS-RC-2 and 786-O cells were cultured in 1% O2 or normal oxygen. Cell proliferation, migration, and invasion abilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, transwell migration, and invasion assays, respectively. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-346 and N-myc downstream-regulated gene 2 (NDRG2). Then bioinformatics analysis, dual-luciferase reporter assay, and RNA immunoprecipitation were carried out to determine the relationship between miR-346 and NDRG2. The protein expression of NDRG2 was detected by western blot assay. Hypoxia promoted cell proliferation, migration, and invasion in OS-RC-2 and 786-O cells. Meanwhile, we found that miR-346 was upregulated in RCC cells under hypoxia as relative to normoxia. miR-346 deletion could decrease the viability, migration, and invasion abilities of RCC cells under hypoxia. Besides, our data demonstrated that NDRG2 was a target gene of miR-346. The expression of NDRG2 in OS-RC-2 and 786-O cells was lower under hypoxia than under normal oxygen conditions. Moreover, NDRG2 overexpression could inhibit cell proliferation, migration, and invasion in RCC cells under hypoxia. And NDRG2 silencing reversed the inhibitory effects of the miR-346 inhibitor on the viability, migration, and invasion abilities of RCC cells in hypoxia conditions. miR-346 promoted the viability, migration, and invasion of RCC cells under hypoxia by targeting NDRG2.

[Performance of human papillomavirus typing test in cervical precancer lesions and cervical cancer screening].

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

[Effect of transition zone index on the outcome after transurethral resection of prostate].

Objective: To investgate the effect of properative transitional zone index (TZI) on the outcome of transurethral resection of prostate (TURP). Methods: A retrospective analysis was performed on 206 patients with TURP who were admitted to our hospital from January 2016 to September 2018. All patients underwent transrectal ultrasound (TRUS) to determine the total prostate volume (TPV) and the transition zone volume (TZV). Patients were divided into two groups according to TZI (TZV/TPV) (group A: TZI<0.5, group B: TZI≥0.5). We collected data 6-months after surgery including international prostate symptom score (IPSS), quality of life score (QOL), maximum flow rate (Qmax), and postvoiding residue (PVR) to compare the difference of the postoperative outcome of two groups, while the IPSS was subdivided into voiding (IPSS-v) and storage(IPSS-s) symptoms, and the changes of IPSS, IPSS-v, IPSS-s, QOL, Qmax and PVR before and after surgery were analyzed. The treatment efficacy was determined as the changes of IPSS (post/preoperative IPSS: %IPSS), QOL (preoperative QOL-postoperative QOL: ΔQOL) and Qmax(preoperative Qmax-postoperative Qmax: ΔQmax). Pearson linear correlation analysis was employed to estimate the correlation of TZI and %IPSS, ΔQOL and ΔQmax, respectively. Results: A total of 126 patients were in Group A, and 80 patients were in group B. 1. The preoperative clinical data of the two groups were compared. There were no significant differences regarding age, IPSS, IPSS-v, IPSS-s, QOL, Qmax, and PVR between two groups (all P>0.05). However, the TPV of patients in group B (74.57±29.25) ml was significantly larger than that in group A (46.25±24.56) ml, P<0.001. While the postoperative follow-up outcomes of the two groups were compared, we found that IPSS-s (P=0.079), QOL (P=0.710), and PVR (P=0.651) were not statistically different between the two groups, but the postoperative IPSS, IPSS-v, and Qmax (8.50±5.75 vs 6.38±4.36, 4.03±3.75 vs 2.63±2.5, and (16.54±4.43) ml/s vs (18.94±4.84) ml/s, all P<0.05) were significantly different between the two groups. 2. Postoperative IPSS, IPSS-v, IPSS-s, QOL, Qmax and PVR were significantly different from those before surgery in two groups, respectively. 3. Pearson linear correlation analysis showed a significant positive correlation between TZI and ΔQmax (r=0.32, P<0.01), a weaker negative correlation between TZI and %IPSS (r=-0.22, P<0.01), and no correlation between TZI and ΔQOL (r=0.08, P=0.238). Conclusion: There may be a correlation between the outcome of TURP and TZI, and the outcome of TURP may be better in patients with TZI ≥ 0.5.

[The role of Wnt/ß-catenin/TCF-4 pathway on biological behavior of renal cell carcinoma and its mechanism].

Objective: To investigate the role of Wnt/ß-catenin/TCF-4 pathway in renal cancer cells and to analyze its possible mechanism. Methods: ß-catenin and TCF-4 were inhibited by siRNA in 786-O cells. The proliferation of transfected cells was detected by CCK8. The cell death of transfected cells was detected by acridine orange -ethidium bromide staining. The expressions of TCF-4, bcl-2, bax and Caspase-3 were detected in transfection group, empty vector group and negative control groups by western blot. Results: The cell proliferation ability of the ß-catenin transfection group was significantly lower than that of the control group (0.443±0.145 vs 0.910±0.721), meanwhile, the cell death rate was significantly increased (16.38±5.32 vs 6.61±1.04), the expression level of Caspase 3 and bax was increased, and the expression of anti-apoptotic protein Bcl-2 was decreased. Decreased TCF-4 led to the same results as inhibition of ß-catenin (all P<0.05). Conclusion: The Wnt/ß-catenin/TCF-4 pathway may play a role in the regulation of proliferation and apoptosis in 786-O renal cancer cells. The mechanism might through regulating of the downstream apoptosis proteins Caspase 3, bax and anti-apoptotic protein Bcl-2.

Analysis of Consistency between Forensic Psychiatry Identification Diagnosis and Clinical Diagnosis of 1 369 Cases.

ABSTRACT: Objective To explore the consistency between identification diagnosis and pre-identification clinical diagnosis of patients with mental disorder undergoing forensic psychiatry identification. Methods The identification data of 1 369 appraised individuals who underwent criminal responsibility identification carried out by the Forensic Institute of Second Affiliated Hospital of Jining Medical University from 2014 to 2017 were collected retrospectively using self-designed investigation data sorting table. A comparative analysis of the mental disorder diagnosis results of expert opinion and past clinical diagnosis results was made. Results Among 1 369 appraised individuals, 964 cases （70.4%） were identified and diagnosed with mental disorder and 405 cases （29.6%） without mental disorder. Among the former, 63.3% （610 cases） were clinically diagnosed, which was higher than 43.2% （175 cases, P<0.05） in the latter. Among the various mental disorders that had been identified and diagnosed, patients with hysteria, stress, and neurosis had the highest proportion of clinical diagnoses （86.7%）, while patients with mental retardation had the lowest proportion of clinical diagnoses （9.6%）. Schizophrenia had the highest overall consistency rate of identification diagnosis and clinical diagnosis （98.4%）, while personality and behavior disorder had the lowest （33.3%）. The overall consistency rate between clinical diagnosis and identification diagnosis of the mental disorder group was 84.1%, and the Kappa value was 0.759. Compared with clinical diagnosis, the consistency rate between inpatient diagnosis and identification diagnosis was higher （85.9%, P<0.05）. Conclusion In forensic psychiatry identification that provides data of past clinical diagnosis and treatment, a high consistency between identification diagnosis and clinical diagnosis of the appraised individual who is identified and diagnosed with mental disorder exists. Clinical diagnosis （especially the inpatient diagnosis） has a relatively good reference value for forensic psychiatry identification.

Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation.

The prevalence of allergic asthma and incidences of helminth infections in humans are inversely correlated. Although experimental studies have established the causal relation between parasite infection and allergic asthma, the mechanism of the parasite-associated immunomodulation is not fully elucidated. Using a murine model of asthma and nematode parasite Heligmosomoides polygyrus, we investigated the roles of regulatory B cells (Breg ) and T cells (Treg ) in mediation of the protection against allergic asthma by parasite. H. polygyrus infection significantly suppressed ovalbumin (OVA)-induced allergic airway inflammation (AAI) evidenced by alleviated lung histopathology and reduced numbers of bronchoalveolar inflammatory cell infiltration, and induced significant responses of interleukin (IL)-10+ Breg , IL-10+ Treg and forkhead box protein 3 (FoxP3)+ Treg in mesenteric lymph node and spleen of the mice. Adoptive transfer of IL-10+ Breg and IL-10+ Treg cell prevented the lung immunopathology in AAI mice. Depletion of FoxP3+ Treg cells in FoxP3-diphtheria toxin (DT) receptor transgenic mice by diphtheria toxin (DT) treatment exacerbated airway inflammation in parasite-free AAI mice and partially abrogated the parasite-induced protection against AAI. IL-10+ Breg cells were able to promote IL-10+ Treg expansion and maintain FoxP3+ Treg cell population. These two types of Tregs failed to induce CD19+ B cells to transform into IL-10+ Breg cells. These results demonstrate that Breg , IL-10+ Treg and FoxP3+ Treg cells contribute in A discrepant manner to the protection against allergic airway immunopathology by parasiteS. Breg cell might be a key upstream regulatory cell that induces IL-10+ Treg response and supports FoxP3+ Treg cell population which, in turn, mediate the parasite-imposed immunosuppression of allergic airway inflammation. These results provide insight into the immunological relationship between parasite infection and allergic asthma.

A Backcross Line of Thatcher Wheat with Adult Plant Leaf Rust Resistance Derived from Duster Wheat has Lr46 and Lr77.

The widely grown hard red winter wheat cultivar Duster released in 2006 has remained highly resistant to leaf rust caused by Puccinia triticina in the southern Great Plains of the United States. In contrast, many of the winter wheat cultivars in this region are susceptible to leaf rust. The goal of this study was to identify the number and chromosome location of leaf rust resistance genes in a line of Thatcher*2/Duster wheat that was selected for adult plant leaf rust resistance. The Thatcher*2/Duster line was crossed with Thatcher (Tc) and a recombinant line inbred line (RIL) population was advanced to the F6 generation by single-seed descent. The parents and RIL population were phenotyped for leaf rust resistance in three field plot tests and in an adult plant greenhouse test. Single-nucleotide polymorphism (SNP) markers derived from the Illumina Infinium iSelect 90K wheat SNP array, kompetitive allele-specific polymerase chain reaction assays on chromosome 3BL, and a sequence tagged site (STS) marker on chromosome 1BL were used to construct a genetic map of the RIL population. The STS marker csLV46G22 that is linked with resistance gene Lr46 on chromosome 1BL, and SNP marker IWB10344 that is linked with Lr77 on chromosome 3BL, were significantly associated with lower leaf rust severity. Duster has at least three adult plant resistance genes for leaf rust resistance because it was previously determined to also have the adult plant resistance gene Lr34. Duster is a valuable source of durable leaf rust resistance for hard red winter wheat improvement in the Great Plains region.