Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Background Job burnout has become an important factor affecting the mental and physical health and work efficiency of college counselors, and indirectly affects the quality and development of talent cultivation for college students. Objective To explore the relationship between job stress, job crafting, and job burnout among college counselors, and to test the mediating role of job crafting between job stress and job burnout, in order to take targeted measures to alleviate job stress and job burnout of college counselors, reduce associated health risks, and improve the effectiveness of higher education. Methods An anonymous questionnaire survey was conducted among 400 counselors from social network communication groups by convenience sampling. The Counselor Work Stress Scale, Job Crafting Scale, and Maslach Burnout Inventory-General Survey were used. Harman's single-factor method was used to evaluate common method bias in the survey data. One-way ANOVA was applied to test the difference in job stress, job crafting, and job burnout among college counselors by demographic characteristics, and chi-square test was used to analyze the difference in reporting job burnout. Partial correlation analysis was used to evaluate the correlation between selected variables. Structural equation modeling was used to analyze the relationship of job stress, job crafting, and job burnout among college counselors, and Bootstrap analysis was used to test if there was a mediating effect of job crafting on the relationship between job stress and job burnout. Results Of the 390 questionnaires recovered, there were 338 valid questionnaires (86.67%). Among the included subjects, the mean scores of job stress, job crafting, and job burnout were (2.70±0.62), (3.77±0.62), and (2.09±1.09), respectively. The positive rate of job burnout was 76.9% (260/338), with a positive rate of 72.8% in exhaustion dimension and 59.8% in cynicism dimension. There were significant differences in job crafting scores among the college counselors by different genders and professional titles (P<0.05). Female counselors had significantly higher job burnout scores and positive rates than male counselors (P<0.05). The partial correlation analysis showed that job stress, work load, school evaluation and expectation, and interpersonal relationship were positively correlated with job burnout (r=0.562, 0.442, 0.473, and 0.455, respectively, P<0.01), and negatively correlated with job crafting (r=−0.271, −0.169, −0.246, and −0.247, respectively, P<0.01); job crafting, cognitive crafting, relationship crafting, and task crafting were negatively correlated with job burnout (r=−0.447, −0.452, −0.366, and −0.340, respectively, P<0.01). The modified structural equation modeling indicated that job stress negatively affected job crafting (b=−0.348, P<0.001) and positively affected job burnout (b=0.454, P<0.001); job crafting negatively affected job burnout (b=−0.459, P<0.001), and played a partial mediating role in the relationship between job stress and job burnout, and the effect value was 0.160 (95%CI: 0.102, 0.230) that accounted for 26.10% of the total effect. Conclusion Job burnout among the college counselors is prominent. Job crafting presents an inhibitory effect on job burnout. Job stress indirectly affects the occurrence of job burnout by inhibiting the generation of job crafting.

BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

BACKGROUND: The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF. METHODS & RESULTS: We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively. CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Objective Network pharmacology and molecular docking and molecular dynamics techniques were used to investigate the mechanism of action of Alhagi sparsifolia Shap.in the treatment of sepsis and to perform animal experimental verification.Methods First,we screened the effective ingredients and their action targets of Alhagi sparsifolia Shap.,meanwhile,screened relevant action targets for the treatment of sepsis,constructed a protein interaction(PPI)network,and performed topology analysis to draw a TCM disease target network diagram.Second,Kyoto Encyclopedia of genes and genomes enrichment analysis was performed for core targets in the network diagram,along with gene ontology functional enrichment analysis.This was followed by molecular docking and molecular dynamics simulation experiment validation of the core targets.Finally,mice were used for the verification of animal experiments.Results Thirty active components of Alhagi sparsifolia Shap.were screened out,and the top 5 ranked by degree value were quercetin,(-)-epigallocatechin,(-)-Epigallocatechin Gallate,genistein,kaempferol and epigallocatechin with 196 action targets;2144 disease-related targets for sepsis,105 targets for Alhagi sparsifolia Shap.-sepsis intersection,and the core targets were TNF,IL-6,AKT1,VEGFA,CASP3,IL-1β Et al.PI3K-Akt,TNF,HIF-1,AGE-RAGE,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert therapeutic effects on sepsis.Molecular docking results showed that camelina flavanoids bound equally well to each key target,among which the conformations with the lowest binding energy were(-)-Epigallocatechin Gallate-IL-6 and quercetin-IL-6.Molecular dynamics simulations were performed on the two pairs of complexes,and the results indicated that the stable binding could be achieved through a combination of electrostatic,van der Waals potential,and hydrogen bonding interactions.Animal experiments confirmed that Alhagi sparsifolia Shap.could inhibit the activation of PI3K/Akt signaling pathway,decrease the protein expression of Caspase-3,VEGF and reduced peripheral blood inflammatory factors secretion of TNF-α、IL-1βand IL-6,alleviating inflammatory injury in tissues and organs.Conclusion The therapeutic effect of Alhagi sparsifolia Shap.on sepsis is achieved through multi biological processes,multi targets,and multi pathways.It provides a certain theoretical basis for the clinical application of camel spines as well as sepsis treatment.

Objective : The purpose of this study was to investigate the effects of plasma exosome⁃derived miR⁃29b⁃3p in myocardial ischemia⁃reperfusion injury ( MIRI) rats on hypoxia/reoxygenation ( H/R) cardiomyocyte after sevoflurane (SEV) postconditioning through targeting IGF1 . Methods : The GEO database was used to screen differentially expressed miRNAs in MIRI , and cardiomyocytes were treated with H/R to construct a MIRI cell model. The expression of miR⁃29b⁃3p and IGF1 in the MIRI cell model post⁃treated with SEV was intervened , and then the survival rate of cardiomyocytes was detected by MTT , apoptosis was detected by flow cytometry , and inflammatory factors (IL⁃1β and TNF⁃α ) in cardiomyocytes in each group were detected by ELISA. Results : Compared with Normal group , the expression of miR⁃29b⁃3p in plasma exosomes of MIRI rats was enhanced (P < 0. 05) , and the target⁃binding relationship between miR⁃29b⁃3p and IGF1 was confirmed ( P < 0. 05) . After SEV post⁃treatment , the expression of miR⁃29b⁃3p in H/R⁃stimulated cardiomyocytes decreased , while the expression of IGF1 increased (both P < 0. 05) . Overexpression of miR⁃29b⁃3p in plasma exosomes could significantly inhibit the survival rate of H/R cells after SEV treatment , aggravate apoptosis and inflammatory response , while knockdown of miR⁃29b⁃3p showed a opposite effects (all P < 0. 05) . The rescue experimental data showed that overexpression of IGF1 could partially reverse the effects of overexpression of miR⁃29b⁃3p on H/R cell injury after SEV treatment ( all P <0. 05) . Conclusion Plasma exosome⁃derived miR⁃29b⁃3p promotes H/R cardiomyocyte injury after SEV treatment by targeting IGF1 .

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy with TRIANGLE operation in the treatment of pancreatic head cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 51 patients with pancreatic head cancer who were admitted to the Sichuan Provincial People′s Hospital, Affiliated Hospital of School of Medicine of University of Electronic Science and Technology of China from January 2017 to July 2018 were collected. There were 33 males and 18 females, aged from 42 to 74 years, with a median age of 56 years. Of the 51 patients, 24 cases undergoing standard pancreaticoduodenectomy, in which No.12, 13 and 17 lymph nodes were dissected, combined with transcatheter arterial infusion chemo-therapy (TAI) were allocated into the standard group, and 27 cases undergoing pancreaticoduo-denectomy with TRIANGLE operation, in which No.7, 8, 9, 12, 13, 16, 17 lymph nodes were dissected, combined with TAI were allocated into the TRIANGLE group, respectively. Observation indicators: (1) intraoperative conditions of the two groups; (2) postoperative conditions of the two groups; (3) follow-up and survival. Follow-up was conducted using outpatient examination and telephone interview once three months to detect tumor recurrence and metastasis and survival of patients up to July 2021 or the death of patient. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the chi-square test or the Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan‐Meier method was used to calculate the survival rate and median survival time and draw survival curve. Log‐Rank test was used for survival analysis. Results:(1) Comparison of intraoperative conditions between the two groups. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion were (501±61)minutes, (563±278)mL, 4 in the standard group, versus (556±46)minutes, (489±234)mL, 6 in the TRIANGLE group, respectively. There was a significant difference in the operation time between the two groups ( t=3.62, P<0.05) but there was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups ( t=1.03, χ2=0.25, P>0.05). (2) Comparison of postoperative conditions between the two groups. Of the 51 patients, 30 had 50 times of postoperative complications, including 18 times of grade Ⅰ complications of Clavien-Dindo classification, 29 times of grade Ⅱ complications of Clavien-Dindo classification, 2 times of grade Ⅲa complications of Clavien-Dindo classification, 1 time of grade Ⅲb complications of Clavien-Dindo classification, respectively. Cases with postoperative complications, cases with delayed gastric emptying, cases without or with pancreatic fistula as class A or class B, cases with biliary fistula, cases with bleeding, cases with diarrhea were 15, 4, 13, 7, 4, 4, 2, 2 in the standard group, versus 15, 6, 14, 10, 3, 4, 1, 3 in the TRIANGLE group, respectively. There was no significant difference in cases with postoperative complications, cases with delayed gastric emptying, cases with pancreatic fistula between the two groups ( χ2=0.16, 0.02, Z=-0.04, P>0.05) and there was no significant difference in cases with biliary fistula, cases with bleeding, cases with diarrhea between the two groups ( P>0.05). Cases with complications as Clavien-Dindo grade Ⅰ, grade Ⅱ, grade Ⅲ were 10, 11, 2 in the standard group, versus 8, 18, 1 in the TRIANGLE group, showing no significant difference between the two groups ( Z=-0.67, P>0.05). The duration of postoperative hospital stay was (23±8)days in both of the standard group and the TRIANGLE group, showing no significant difference between the two groups ( t=0.31, P>0.05). (3) Follow-up and survival. All the 51 patients were followed-up for 6 to 54 months, with a median follow-up time of 17 months. The postoperative 1-year overall survival rate was 75.0% and 81.5% in the standard group and the TRIANGLE group, respectively. The postoperative 3-year overall survival rate was 12.5% and 22.2% in the standard group and the TRIANGLE group, respectively. The median postoperative survival time was 15.00 months (95% confidence interval as 12.63 to 17.37 months) and 21.00 months (95% confidence interval as 15.91 to 19.62 months) in the standard group and the TRIANGLE group, respectively. There was a significant difference in survival of patients between the two groups ( χ2=4.30, P<0.05). Cases with tumor recurrence during post-operative 1 year and 3 year were 9 and 20 in the standard group, versus 6 and 15 in the TRIANGLE group, respectively. There was no significant difference in cases with tumor recurrence during postoperative 1 year between the two groups ( P>0.05) and there was a significant difference in cases with tumor recurrence during postoperative 3 year between the two groups ( P<0.05). Conclusion:Compared with standard pancreaticoduodenectomy, pancreaticoduodenectomy with TRIANGLE operation can prolong the median survival time of patients with pancreatic head cancer without increasing surgical related complications.

Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.

Objective （ ） To explore the application value of bone suppression imaging BSI in the diagnosis of occupational （ pneumoconiosis） Methods - pneumoconiosis hereinafter referred to as " " . A total of 330 chest films of high kV digital （ ） radiograph DR of patients with suspected pneumoconiosis were selected by convenient sampling method. BSI is applied to the ， ， ， ， chest films and the differences of small opacity shape small opacity aggregation the number of large opacity lung areas small （ ）， opacity profusion and diagnostic stage of pneumoconiosis were analyzed by simple DR reading DR group simple BSI reading （ ） （ ） Results BSI group and DR and BSI combined reading combined group . There was no significant difference in the distribution of small shadows and the detection rate of small shadows aggregation and large shadows in pneumoconiosis among （ P ） ， the three film reading methods all >0.05 . For the concentration distribution of each lung area there was statistically （P< ）， significant difference between the DR group and the BSI group 0.05 but there was no statistically significant difference ， （ P ） between the DR group and the combined group and between the BSI group and the combined group all >0.05 . The results of ， consistency analysis showed that the DR group and the BSI group and the DR group and the combined group had high （ ， P< consistency in the judgment of small shadow intensity in the lung region both weighted Kappa coefficient were 0.75 all ） 0.01 . There was a high consistency between BSI group and DR group and combined group and DR group in the diagnosis of （ ， ， P< ） ， pneumoconiosis stage weighted Kappa coefficient were 0.77 0.79 all 0.01 . Compared with the DR group the diagnostic ， rate of pneumoconiosis stage Ⅰwas significantly reduced and the diagnostic rate of pneumoconiosis stage Ⅱ was significantly （ P< ） ， increased in the BSI group and the combined group all 0.01 . However there was no significant difference in the diagnosticrate of pneumoconiosis stage Ⅲ >0.05 . Both the BSI reading and DR and BSI combined reading can improve ， the display of pneumoconiosis lesions to varying degrees and therefore can improve the diagnosis of pneumoconiosis. In ， addition the identification and diagnosis of pneumoconiosis lesions in the BSI reading is comparable to that in the combined ， group which has a good application value in the diagnosis of pneumoconiosis.