The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88％on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66％on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.

Cell Cycle Checkpoints/genetics* ; Checkpoint Kinase 1/metabolism* ; Heterozygote ; Humans ; Mitosis/genetics* ; Mutation ; Zygote/metabolism*

Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t -test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P =0.148), ORR (36.7% vs 18.5%, P =0.098), DCR (65.3% vs 55.6%, P =0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P =0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Objective:To study the relationship between the relevant chemical elements in the original surface drinking water sources and the prevalence of dental fluorosis in Bijie City, Guizhou Province, and to provide a scientific basis for further studying the distribution of dental fluorosis patients, clarifying the mechanism of endemic fluorosis, and scientifically adjusting relevant prevention and treatment policies.Methods:From August 2021 to March 2022, based on the local census data of endemic fluorosis in Guizhou Province, 385 samples of original surface drinking water sources were collected in 214 townships (towns) of Bijie City. The pH value, and contents of fluorine (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), manganese (Mn), copper (Cu), zinc (Zn), nickel (Ni), arsenic (As), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb), chromium (Cr), iron (Fe), and selenium (Se) in the drinking water were determined. Taking the dental fluorosis index representing the prevalence of dental fluorosis as the dependent variable, a principal component multiple regression model was constructed based on the above chemical elements of drinking water to study the related factors affecting the prevalence of dental fluorosis, and its contribution rate was calculated.Results:The median of dental fluorosis index in 214 townships (towns) of Bijie City was 1.460. The average of pH values and contents of F, Ca, Mg, Al, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Cd, Ba and Pb of 385 drinking water samples were 6.369, and 0.209, 179.706, 16.198, 0.163, 0.987, 0.015, 0.073, 0.176, 0.027, 0.014, 0.191, 0.007, 0.005, 0.003, 0.001, 0.155, 0.005 mg/L, respectively. Six principal components ( F1 - F6) were extracted by principal component regression analysis, and the cumulative contribution rate was 72.05%. After multiple linear regression analysis, the chemical elements in drinking water were positively correlated with the prevalence of dental fluorosis in the order of Se, Fe, Cr, Mn, Ni, Cd and Cu, and negatively correlated with the prevalence of dental fluorosis in the order of Ba, F, Ti, Mo, Zn, Al, Pb, Ca, As and Mg. Conclusions:The chemical properties in drinking water of endemic fluorosis areas in Bijie City have obvious synergistic or antagonistic effects on the occurrence and prevalence of dental fluorosis in this area. The F in the drinking water may not play a decisive role in the occurrence and prevalence of local dental fluorosis.

Objective:To investigate the role of KLF4 in lipopolysaccharide induced cardiomyocyte injury.Methods:Primary rat cardiomyocytes were isolated and cultured, and randomly divided into 5 groups: control group, negative control (NC), LPS group, KLF4 overexpression group, KLF4 overexpression+LPS group. MTT method was used to detect cell activity, ROS, SOD 2, GPX and MDA were detected by kit, TNFa, IL-1 β and IL-6 were detected by ELISA. TUNEL staining was used to detect apoptosis. The protein levels of TLR4 and Nrf2 were detected by Western blot.Results:The expression of KLF4 in cardiomyocytes was significantly higher than that in the NC group ( P<0.001). The cell activity of LPS group was significantly lower than that of NC group ( P < 0.001), and that of KLF4 overexpression +LPS group was higher than that of LPS group ( P<0.001). The levels of TNFa, IL-1 β and IL-6 in LPS group were significantly higher than those in the NC group ( P<0.0001), and the levels of TNFa, IL-1 β and IL-6 in KLF4 overexpression +LPS group were lower than those in LPS group ( P<0.0001). The levels of ROS and MDA in LPS group were significantly higher than those in the control group, while the activities of SOD2 and GPX were lower than those in the NC group ( P<0.0001); the levels of ROS and MDA in KLF4 overexpression +LPS group were lower than those in LPS group, while the activities of SOD2 and GPX were higher than those in LPS group ( P<0.0001). The number of apoptosis in LPS group was significantly higher than that in the NC group, and that in KLF4 overexpression +LPS group was lower than that in LPS group ( P< 0.001). The level of TLR4 wan higher and Nrf2 protein in the nucleus of LPS group was lower than that of the NC group. The level of TLR4 was lower and Nrf2 protein in the nucleus of KLF4 overexpression+LPS group was significantly higher than that of LPS group ( P < 0.001). Conclusions:KLF4 can alleviate LPS induced cardiomyocyte injury by regulating TLR4 and NRF2 signals.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Objective To investigate the role of anaphylatoxin C3a on epithelial mesenchymal transition(MTT) in normal human bronchial epithelium cells and its molecular mechanism.Methods Normal human bronchial epithelium cells BEAS-2B were cultured,and divided into control group,rhC3a stimulation group,rhC3a+ C3a receptor(C3aRA)antagonist group,the morphological changes of cells were observed by microscope;cell proliferation was detected by MTT;the expression of TGF-β1 protein level in cell supernatant was evaluated by ELISA;the expression of C3aR mRNA and EMT related indicators mRNA changes were detected by RT-PCR;the expression of C3aR and Smad2/3,p38 MAPK pathway proteins were detected by Western blot.Results Cell morphology in 30,50 nmol/L rhC3a stimulation group was changed from normal cobblestone like to spindle shape,cell morphology in C3aRA antagonist group had no significant change when compared with the control group.The cell proliferation was reduced in 50 nmol/L rhC3a stimulation group(P=0.047);the levels of TGF-β1,p-Smad2/3,p-p38-MAPK protein were increased(P＜0.05),C3aR mRNA and protein levels were also significantly increased (P＜0.05) in 30 nmol/L rhC3a stimulation group when compared with control group,but the addition of 1 μmol/L C3aRA could reduce their expressions(P＜0.05).30 nmol/L rhC3a could induce the up regulation of α-SMA and N-cadherin mRNA,and decrease the expression of E-cadherin mRNA,adding 1 μmol/L C3aRA can antagonize this process (P＜0.05).Conclusion Anaphylatoxin C3a can induce EMT in normal human bronchial epithelium cells by combining C3aR,its mechanism may be involved in activating Smad2/3 and p38-MAPK pathway.

Objective To explore the role of the PI3K/Akt signaling pathway in the calvarial osteolysis induced by TCP wear particles in mice model.Methods Thirty-six male ICR mice were randomly divided into a sham group (n=12),TCP group (n=12)and a LY294002-treated group (n=12).A murine calvarial model of osteolysis was established through implanting 30 mg of TCP particles onto the surface of bilateral parietal bones following the removal of the periosteum.On the second postoperative day,LY294002 (5 mg·kg-1)was locally injected to the calvarium under the periosteum three times a week;mice in the sham group received local injection of normal saline (N.S.)in the calvarium,and the injection time was consistent with that of LY294002.Two weeks later,the calvaria and periostea were obtained after the mice were executed.The calvarial osteolysis,bone mineral density (BMD)and bone mineral content(BMC)were analyzed using Micro-CT,Hematoxylin-Eosin (HE)staining was conducted to observe the inflammatrory response and formation of osteoclasts.Real-time PCR was applied to detect the mRNA level of tartrate-resistant acid phosphatase (TRAP),the marker of osteoclasts formation,cathepsin K (CstK),receptor activator for nuclear factor-κB kigand (RANKL)and c-Fos.The release of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and IL-1β were measured using enzyme-linked immumsorbent assay (ELISA).Results Micro-CT and histological analysis indicated that LY294002,the specific inhibitor of PI3K,significantly prevented TCP wear particles-induced osteolysis and osteoclastogenesis,and increased BMD and BMC in the calvaria of mice.Real-time PCR data revealed LY294002 significantly suppressed the increase in mRNA level of osteoclastogenic genes such as TRAP,CstK,RANKL and c-Fos in the calvaria of TCP wear particles-implanted group.ELISA assay showed that TCP wear particles-induced release of TNF-α,IL-1β and IL-6 was significantly inhibited by LY294002 treatment.Furthermore,LY294002 significantly attenuated TCP wear particles-triggered activation of Akt,and down-regulated the level of p-AktSer473 and p-AktThr308.Conclusion PI3K/Akt signaling pathway contributes to TCP wear particle-induced osteolysis,and can be developed as a new therapeutic target for the prevention and treatment of bone destruction diseases caused by wear debris.