Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective:To determine the accuracy and clinical application of donor HLA quartile genotyping based upon transplanted kidney biopsy.Methods:The clinical and follow-up data are retrospectively reviewed for 38 recipients of kidney transplantation(KT)at First Affiliated Hospital of Xi'an Jiaotong University from 2019 to 2022.They are suspected of rejection.HLA quartile genotyping of donor kidney is performed through puncture and DNA analysis by LABType SSO method.Known HLA genotypes of recipients are compared for predicting HLA genotypes of donors.Donor-specific antibody(DSA)is detected by Labscreen Single kit.And SPSS18.0 statistical software is employed for processing baseline data, donor/recipient HLA typing data, recipient DSA antibody data and transplant nephropathy parameters.Results:Among them, 12(31.58%)belonged to HLA-A, B, C, DR and DQ.Four loci are detected in 14 cases(36.84%). Three sites are detected in 10 cases(26.32%). Two sites are detected in 2 cases(5.26%)and a negative correlation exists between detected sites and transplantation time( rs=-0.707, P=0.001). The detection rate of HLA loci is 78.94%(30 cases). B: 65.78%(25 cases); C: 84.21%(32 cases); DR: 57.89%(22 cases); DQ: 100% (38 cases); HLA sites detected in puncture tissue are 89.47% consistent with the results of donor whole blood test, among which HLA-C and HLA-DQ sites are 100% consistent and HLA-A and HLA-B sites 87.50% and 90% consistent and HLA-DR sites 66.7% consistent( P<0.01). Spearman's rank correlation analysis indicated that pathological diagnosis of interstitial inflammation( rs=-0.432, P=0.017), renal tubule atrophy( rs=-0.587, P=0.001)and interstitial fibrosis( rs=-0.560, P=0.001)are correlated negatively with HLA detected sites in transplanted kidney puncture tissue.DSA is detected in 42.1% of recipients and 68.75% of recipients belonged to HLA-DQ. Conclusions:HLA typing results of puncture tissue are consistent with those of whole blood test.Time after transplantation, infiltration of transplanted nephritis cells and degree of fibrosis may influence the detection of HLA loci.Donor HLA quartile genotyping using transplanted kidney biopsy has some diagnostic values for detecting the presence of DSA.

Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.

This article introduces the contents of the latest edition Risk of Bias in Non-randomized Studies-of Exposure (ROBINS-E) published in June 2022 [ROBINS-E (2022)], and gives some examples about its usage. ROBINS-E is a tool for assessing the risk of bias in non-randomized studies-of exposure. Compared with ROBINS-E (2019), ROBINS-E (2022) adds more bias for observational studies, covers a more comprehensive range of bias, and adds the assessment of the external authenticity of the study. ROBINS-E (2022) adds a preliminary evaluation process to improve the efficiency of evaluation. In addition, ROBINS-E (2022) visualizes and instrumentalizes the use of signal problems in the form of path graph, making it more convenient to use. ROBINS-E (2022), although more consideration has been given to the issue of co-exposure, still does not address the problem of effect modification in co-exposure, and there is still room to expand the applicable research.

The immune mechanism of chronic hepatitis B (CHB) persistent infection is closely associated with T cells, and the development of T cells requires the coordination of a variety of cytokines. The proteins of the signal transducer and activator of transcription (STAT) family are mainly involved in the signal transduction of cytokines, and STAT5a/b and STAT3 play an important role in the differentiation and development of regulatory T cells (Treg) and T helper 17 cells (Th17). This article analyzes the association of STAT3 and STAT5 with Treg/Th17 balance in CHB and investigates the chronicity of hepatitis B virus infection and the regulatory mechanism of liver inflammation.

Objective:To investigate the knowledge, attitude and practice of adult oxygen inhalation therapy among nurses and analyze its influencing factors.Methods:A self-designed questionnaire was used to investigate the status of knowledge, attitude and practice of adult oxygen inhalation therapy among 1 410 nurses from many tertiary, secondary and lower hospitals in Chongqing, Jiangsu, Sichuan, Shanxi and other provinces and cities from December 2020 to January 2021 by convenient sampling method.Results:The score of nurses′ knowledge of adult oxygen inhalation therapy was 1-39 (23.10 ±4.82) points, the standard score was (44.42 ±9.27) points, the score of excellent was 0, the score of moderate was 1.8%(25/1 410), the score of poor was 98.2%(1 385/1 410). The score of nurses′ attitude of adult oxygen inhalation therapy was 6-30 (25.06 ±4.37) points, the standard score was (83.53 ±14.58) points, positive attitude accounted for 42.9%(605/1 410), neutral attitude accounted for 54.6%(770/1 410), negative attitude accounted for 2.5%(35/1 410). The score of nurses′ practice of adult oxygen inhalation therapy was 9-54 (33.82 ±6.32) points, and the standard score was (75.12 ±13.99). Positive practice accounted for 21.2%(299/1 410), neutral practice accounted for 70.4%(993/1410) points, negative practice accounted for 8.4%(118/1 410). The knowledge and attitude of nurses to adult oxygen inhalation therapy were positively correlated with practice( r=0.193, 0.554, both P<0.01). Multiple linear regression analysis showed that nurses′ knowledge, attitude and training frequency were the influencing factors of adult oxygen inhalation therapy practice( t=3.17, 23.33, 8.64, all P<0.01). Conclusions:Nurses should strengthen the study and training of adult oxygen inhalation therapy, correct attitude and improve practice, reduce or avoid the occurrence of excessive oxygen therapy and oxygen therapy complications, standardize clinical oxygen therapy to ensure the safety and effectiveness of oxygen therapy.

The regulatory T cells (Treg) and helper T cells 17 (Th17) play an important role in regulation of the tumor microenvironment in hepatocellular carcinoma (HCC) because Treg/Th17 imbalance was associated with HCC cell invasion and progression. Moreover, the suppressor of cytokine signaling 1 (SOCS1), a negative regulator of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, regulates Treg and Th17 proliferation and differentiation. This review summarized and discussed the recent advancement and progress in control of the Treg/Th17 balance in HCC and the immunity-related mechanisms in HCC development and progression, i.e., the SOCS1 structure and functions, SOCS1 role in regulation of Treg/Th17 balance in HCC, and future research direction of the field.

Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.
Humans ; Osteoblasts ; Osteoclasts ; Periodontal Ligament ; Periodontium ; Root Resorption ; Tooth Movement Techniques

Objective:To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles.Methods:The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate.Results:A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn >2 250 U, with no significant difference between them ( P=0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant ( P=0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups ( P=0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found ( P=0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups ( P=0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant ( P=0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate ( P>0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant ( OR=1.031, 95 %CI: 1.010-1.054, P=0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy ( OR=0.981, 95 %CI: 0.971-0.991, P<0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups ( P=0.613, P=0.738, P=0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P>0.05). Conclusions:In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.