Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560) Conclusions Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.

OBJECTIVE To investigate effects of children with allergic rhinitis on physical and mental condition of their family caregivers.METHODS The family caregivers of 149 children with allergic rhinitis were enrolled,and fatigue,anxiety and depression scales were investigated and risk factors were analyzed through questionnaires.RESULTS The symptoms of fatigue,anxiety and depression in family caregivers were more frequent in family caregivers whose children had more severe symptoms of allergic rhinitis(r=0.426,P=0.000;r=0.479,P=0.000;r=0.358,P=0.000).Family caregivers with children aged＜3 years or with other allergic diseases combined had higher levels of fatigue(P=0.000,P=0.000),anxiety(P=0.000,P=0.000)and depression(P=0.003,P=0.001),while the family caregivers of children with perennial/persistent symptoms had higher levels of depression(P=0.021).The degree of fatigue,anxiety and depression in females was significantly higher than that in males(P=0.032,P=0.018,P=0.021).CONCLUSION Children with allergic rhinitis in children had significant impact on the fatigue,anxiety and depression of their family caregivers.The symptoms of fatigue,anxiety and depression were related to age of children,characteristics of disease,whether they were combined with other allergic diseases,and gender and education level of the family caregivers.

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

Objective:To compare the biomechanical properties of traditional surface hip prosthesis and bionic surface hip prosthesis.Methods:The Sawbone digital model (#3908, Left, Medium) was selected as the research object. Mimics 21.0 software was used to reconstruct the physical model of femur. Solidworks 16.0 software was used to build the model of prostheses, including the traditional and bionic (type 1-4) protheses and their assembly. The distances from the screw cross position to the top of pressure screw of type 1 to type 4 protheses were 20.22 mm, 30.12 mm, 32.17 mm and 37.76 mm, respectively. The mechanical distribution characteristics of the whole model were measured and the stress distribution cloud map was obtained.Results:The peak stresses at bone-stem junction of traditional prosthesis and type 1-4 hip prostheses were 32.18 MPa, 13.80 MPa, 15.01 MPa, 23.46 MPa and 34.51 MPa, respectively. With the fulcrums away from the top of the femur, the peak stresses at the fulcrums of type 1-4 hip protheses were 37.98 MPa, 48.60 MPa, 54.80 MPa, and 53.87 MPa, respectively. The maximum stress above femoral neck of traditional prosthesis and type 1-4 hip prostheses were 8.00 MPa, 7.80 MPa, 7.04 MPa, 7.03 MPa and 7.51 MPa, respectively. The maximum stresses under femoral neck was 15.38 MPa, 14.20 MPa, 11.11 MPa, 13.10 MPa and 12.18 MPa, respectively. The maximum stresses in the greater trochanter region of femur were 13.08 MPa, 11.61 MPa, 13.09 MPa, 11.02 MPa and 39.51 MPa, respectively.Conclusion:Compared with the traditional surface hip prosthesis, the type I bionic surface hip prosthesis is designed based on the lever balance reconstruction theory. With the bionic reconstruction of the tension trabeculae and compression trabeculae through reasonable screw placement angles and the inward movement of the fulcrum closer to the center of the femoral head, the new type prothesis make up for the design defects of the traditional surface hip prosthesis, optimize the stress distribution in the proximal femur, and improve the stability of the prosthesis after replacement, which help reduce the risk of femoral neck fracture and prosthesis loosening, and extend the service life of the prosthesis.

OBJECTIVE To evaluate the clinical value of contrast-enhanced ultrasonography (CEUS) in diagnosing thyroid carcinoma.METHODS The clinical data of 129 patients with thyroid nodules,who were examined by CEUS and were operated in Xinhua Hospital between Jan 2014 and Aug 2015,were analyzed in order to compare the diagnostic results of CEUS to the postoperative pathologic findings,and to summarize its imaging features.RESULTS A total of 132 thyroid nodules in 129 patients were examined by CEUS.Among them,103 nodules were diagnosed as thyroid carcinoma,24 nodules were benign thyroid tumor and 5 nodules were thyroiditis.Compared with pathology results,the diagnostic accuracy,sensitivity and specificity of contrast-enhanced ultrasound is 88.6％,92.2％ and of 75.9％ respectively.The diagnosis of the CEUS in 31 cases was not consistent with the pathological results,in which 8 cases of thyroid carcinoma were misdiagnosed as benign tumor,3 cases of thyroiditis were misdiagnosed as thyroid carcinoma,and 20 cases of benign tumors were misdiagnosed as thyroid carcinoma.The malignant thyroid nodules mainly were papillary carcinoma,which was characterized by'low enhanced'and'slow in fast out'performance in the contrast-enhanced ultrasound examination.CONCLUSION The contrast-enhanced ultrasound examination in diagnosing thyroid carcinoma has much more specificity and sensitivity,the'low-enhanced'and'slow in fast out'signs of the CEUS were the important features of malignant thyroid nodules.

Objective To investigate the effect of decitabine (DAC) on human acute myeloid leukemia (AML) cell line HL-60 and the regulating of natural killer (NK) cell activating receptor (NKG2D) ligands(NKG2DL), and to detect the molecular mechanism of JAK-STAT3-SOCS signaling pathway. Methods The effect of DAC on the proliferation of HL-60 was detected by using CCK-8 assay. The cell apoptosis was analyzed by using Annexin-V/PI double standard method. The expressions of receptor NKG2DL including MICA/B and ULBPs in HL-60 cells were detected by using flow cytometry (FCM). The killing activity of NK cells was analyzed by using carboxy fluorescein diacetate succinimidyl ester (CFSE). The expressions of JAK/STAT3 signaling pathway or molecules including STAT3, its upstream kinases JAK1, JAK2 and the negative regulator of STAT3,SOCS-1,SOCS-3 were examined by Western blot.Methylation level of the SOCS-1,SOCS-3 gene after the treatment of DAC was analyzed by using methylation-sensitive high resolution melting(MS-HRM). Results There was an obvious inhibitory effect of DAC on HL-60 cells. The cell viability of HL-60 treated with 0.2, 0.5, and 1.0 μmol/L DAC for 48 h was decreased by (25±11) %, (39±8) % and (50±7)%(P<0.01)respectively compared with those cells without DAC treatment.The incidence of apoptosis was (24.77±7.50) %, (27.10±4.48) % and (30.53±3.93) % after DAC treatment for 48h respectively, which were higher than that of untreated cells[(3.11±0.50)%](P<0.01).DAC induced a significant up-regulation of MICA/B, ULBP-1, ULBP-3 in HL-60 cells, and enhanced the sensitivity of HL-60 cells to NK cytotoxicity. Western blot results showed that a down-regulating expression of STAT3 and JAK1, JAK2 protein was detected, in addition to the phosphor-STAT3 and phosphor-JAKs in HL-60 cells after DAC treatment, but the expressions of SOCS-1 and SOCS-3 protein were increased. HRM results showed that DAC could inhibit the methylation of SOCS-3 gene. Conclusion DAC can inhibit the proliferation of HL-60 cells, upregulate the expression of NKG2DL and enhance the cytotoxicity of NK targeted to HL-60 cells, which might be related to the activity regulation of intracellular JAK-STAT3-SOCS signaling pathway.

Objective To study the cyclooxygenase (COX-2) ,nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF) expression and clinical significance in triple negative breast cancer .Methods From January 2010 to December 2014 ,breast cancer treatment in our hospital 100 patients for the study ,50 patients with triple negative breast cancer ,50 cases of non-triple neg-ative breast cancer was detected by immunohistochemistry ,100 cases of breast cancer were detected by immunohistochemistry in or-ganizations COX-2 ,NF-κB and VEGF expression of lymphatic vessel invasion and lymph vessel density and D2-40 mark detection , statistical analysis of relevant clinical and pathological information .Results COX-2 in triple negative and non-triple negative breast cancer were 76% ,70% ,the difference was not statistically significant (P>0 .05) ,VEGF triple negative breast cancer and non-triple negative breast lesions in cancerous lesions positive expression rates of 60% and 36% ,respectively ,which had significant difference (P<0 .05) .NF-κB in triple negative breast cancer lesions and non-triple negative breast lesions positive expression rate was 66%and 32% ,respectively ,which had significant difference (P< 0 .05) .Triple negative breast cancer NF-κB and VEGF ,COX-2 and VEGF expression was significantly positively related to breast cancer .Conclusion Radiation and chemotherapy is a major means of triple negative breast cancer postoperative treatment ,while inhibiting the NF-κB ,the expression of VEGF and COX-2 is expected to become the new target for treatment of triple negative breast cancer ,is worth exploring .

OBJECTIVETo investigate the molecular mechanism of the growth inhibitory effect of matrine on K562 cells in JAK/STAT3 mediated signal pathway.

METHODSWestern blot analyses were performed to investigate the differential expression of JAK2, STAT3, phosphor-STAT3 (Tyr705 & Ser727) and phosphor-JAK2 proteins after matrine treatment in K562 cells with or without human recombinant interleukin 6 (IL-6) pretreatment. The expression of STAT3 response gene products such as Bcl-xL, Cyclin D1 and c-Myc, were investigated by Western blot and quantitative real time RT-PCR (qRT-PCR). Expression of IL-6, a potent upstream activating factor of JAK/STAT3 pathway, was analyzed by both real time qRT-PCR and ELISA.

RESUTLSWestern blot revealed that matrine treatment resulted in a strong down-regulation of phosphor-STAT3 both in Tyr705 and Ser727 sites or phosphor-JAK2 proteins expression without significant effects on the total STAT3 and JAK2 proteins. The expression of phosphor-Tyr705 STAT3 and phosphor-Ser727 STAT3 was decreased to 0.370 ± 0.172 in K562 cells treated with 0.5 mg/ml matrine for 48 h, respectively, from 0.690 ± 0.119 and 1.150 ± 0.263 in control cells, accompanied with a dramatical down-regulation of phosphor-JAK2 from 0.670 ± 0.137 to 0.049 ± 0.057 (P<0.05). In addition, it was found that the expression of Bcl-xL, Cyclin D1, c-Myc was decreased both at the transcription and protein level in K562 cells after matrine treatment. Matrine treatment resulted in a significant decrease in the expression level of IL-6 in K562 cells from (35.1 ± 1.93) to (10.74 ± 1.83) and (8.66 ± 1.24) pg/ml at the dose of 0.5 and 0.8 mg/ml, respectively (p<0.05). Matrine treatment could diminish the up-regulation of STAT3, JAK2, phosphor-STAT3 and phosphor-JAK2 protein following pretreatment with IL-6 in K562 cells.

CONCLUSIONMatrine exerts its anti-leukemia effect by interfering with the JAK2/STAT3 signaling pathway. The inhibition of IL-6 expression may play a pivotal role in the disruption of JAK/STAT pathway by matrine.

Alkaloids ; Down-Regulation ; Humans ; Interleukin-6 ; Janus Kinase 2 ; K562 Cells ; Quinolizines ; STAT3 Transcription Factor ; Signal Transduction ; Up-Regulation

Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.

OBJECTIVETo probe matrine acting on natural killer cell (NK) activating receptor NKG2D ligands expression in CML cell line K562 and its underlying molecular mechanism.

METHODSThe expression of NKG2D ligands (major histocompatibility complex class I chain-related molecule A or B (MICA/B), UL16-binding proteins (ULBP) 1, 2, and 3 on K562 cells were analyzed before and after treated with matrine by FCM. The cytotoxic sensitivity of K562 to NK cell was detected by FCM after CFSE staining at different effect-to-target (E/T) cell ratios. The expression of signal transduction and transcriptional activator 3 (STAT3) protein as well as phosphorylated STAT3 (p-STAT3) were detected by western blot.

RESULTSAfter treatment with matrine, ULBP1 and ULBP2 expression, especially ULBP2 on K562 cells significantly increased, with mean fluorescence intensity (MFI) increasing to 615 and 1614 by 220 and 615 in the untreated cells, respectively. There was no significant change for MICA or ULBP3 expression. Matrine enhanced the susceptibility of K562 cells to NK-mediated cell lysis. At the ratio of E/T with 5:1, the proportion of the killed K562 cells increased to 32.8%, 38.1% and 40.5%, respectively (after 0.2, 0.5 and 0.8 mg/ml matrine treatment) by 29.2% in the untreated cells. The phosphorylated STAT3 protein, but not STAT3 protein, was significantly inhibited by matrine treatment in K562 cells.

CONCLUSIONMatrine induced the expression of NKG2D ligands in K562cells and enhanced the cytotoxicity of NK cells against K562, which was closely related to the inhibition of STAT3 activity in K562 cell.

Alkaloids ; pharmacology ; GPI-Linked Proteins ; immunology ; Humans ; Intercellular Signaling Peptides and Proteins ; immunology ; K562 Cells ; Quinolizines ; pharmacology ; Signal Transduction ; Up-Regulation ; drug effects