OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85％)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61％to 46.47％.The 5-year relative survival rate increased from 42.1 8％to 51.11％.The 5-year age-standardized relative survival rate increased from 40.57％to 49.80％.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43％of thyroid cancer was the highest,followed by female breast cancer(88.35％)and corpus uteri cancer(85.56％);5.87％of pancreas cancer was the lowest,followed by gallbladder cancer(13.64％)and oesophagus cancer(17.72％).the rate of lung cancer with the largest number of cases was 23.59％,followed by colorectal cancer(59.82％)and stomach cancer(38.65％).The 5-year relative survival rate of total cases of all sites increased from 40.55％in 2002 to 52.77％in 2013,with an average annual percent change of 2.40％.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.

Objective:To investigate the incidence and mortality of ovarian,fallopian tube and other uterine adnexa cancer in 2016 and their trends during 2002 through 2016 in Shanghai. Methods:Data on new ovarian,fallopian tube and other uterine adnexa cancer diagnoses and deaths during 2002 through 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.The incidence and mortality stratified by year of diagnosis or death,site and age-group were analyzed.The number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.Trends in number,age-specific rate,age-standardized rate and others were estimated.Trends in age-standardized rate of incidence and mortality for the ovarian cancer were estimated by Joinpoint analysis and characterized by the annual percent change(APC).The number and proportion of selected indexes of diagnostic characteristics of new ovarian and fallopian tube cancer cases were also calculated.Segi's 1960 world standard population was used for calculating age-standardized rates. Results:The new uterine adnexa cancer cases and deaths were 813 and 440 in Shanghai in 2016.There were 751 cases(92.37％)and 419 deaths(95.23％)of ovarian cancer,and 48 cases(5.91％)and 17 deaths(3.86％)of fallopian tube cancer.The crude rate of ovarian cancer incidence was 10.29/105,and the age-standardized rate was 5.33/105.The crude rate of mortality was 5.74/105,and the age-standardized rate was 2.44/105.Overall,the age-specific rates of incidence and mortality increased with aging.They reached the peak at the age group of 55-59 years and 80-84 years,respectively.Joinpoint analyses showed a significant decreasing trend in the standardized incidence of ovarian cancer in Shanghai from 2002 to 2016,with an average annual increase of 1.78％(APC=-1.78,P＜0.001),while the increase in standardized mortality was not statistically significant.The proportion of pathological diagnosis on ovarian cancer increased to 85.02％,and the proportions of stageⅢ and Ⅳ continued to increase.The incidence of ovarian cancer in Shanghai from 2002 to 2016 showed a decreasing trend,while the mortality showed a fluctuating trend. Conclusion:In Shanghai,the age-standardized incidence rate of ovarian cancer was declined steadily,but the proportion of diagnosed advanced increased.The number of fallopian tube cancer cases increased steadily.

Objective:To describe the long-term characteristics and trend changes in the incidence and mortality of female breast cancer in Shanghai from 1 973 to 2017,aiming to provide references for exploring the etiology of breast cancer and formulating strategies and measures for prevention,intervention and control. Methods:Joinpoint software was used to analyze the trend changes in the incidence and mortality of female breast cancer in Shanghai from 1 973 to 2017,and an age-period-cohort model was constructed to explore the effects of age,year of diagnosis,and birth cohort on long-term trend changes. Results:From 1 973 to 2017,there were 68 192 new cases of female breast cancer in Shanghai,with a diagnosed rate of 31.72/100 000.The incidence rate continued to rise,and the risk of the disease continued to rise from the age of 20 years,and the rise rate accelerated significantly after the age of 40 years.There were 21 535 female breast cancer deaths from 1 973 to 2017.The mortality rate was stable,with a death rate of 8.62/100 000,and the risk of death increased significantly from the age of 45 years.The effects of age,period and cohort had a significant impact on the incidence of breast cancer(P＜0.01),while the increase in mortality rate was related to age and cohort effects(P＜0.01). Conclusion:The incidence rate of female breast cancer in Shanghai is still rising rapidly,and the mortality trend is generally stable,suggesting that the treatment is effective and the quality of life is improved.However,breast cancer is still the main malignant tumor among females in Shanghai.It should be continued to implement prevention and control strategies such as lifestyle intervention and screening of high-risk individuals to further strengthen the prevention and control of breast cancer.

Purpose To evaluate the function of swallowing by examining the relative motion of the hyoid bone and larynx(HL)via ultrasonography,and to explore the value of HL motion ratio in the evaluation of stroke with pharyngeal dysphagia.Materials and Methods A total of 43 stroke patients with dysphagia(dysphagia group)and 43 healthy adults(healthy control group)from June 2021 to April 2022 in the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine and the First Affiliated Hospital of Henan University of Traditional Chinese Medicine were enrolled.The displacement and motion time of HL were measured by ultrasonography when the participants swallowed 5 ml water.The median flow tracking algorithm was implemented in Python language to measure the displacement of the hyoid bone,the movement time of the hyoid bone,the displacement of the larynx and the movement time of larynx,and then HL movement ratio was calculated,respectively.The differences in ultrasonography measurements between the two groups were compared,and the influencing factors of stroke with dysphagia were screened out via Logistic regression analysis.Then the receiver operating characteristic curve was drawn,the area under curve and the cut-off value,sensitivity and specificity were calculated subsequently.Results The larynx motion time(static phase),the larynx displacement(elevation phase)and the HL motion ratio were significantly related to swallowing in healthy participants,with significant differences between the two groups(t=4.97,6.38,6.17,P<0.05).The results of Logistic regression analysis showed that the HL motion ratio was the influencing factor of stroke with dysphagia(OR>1,P<0.05).The optimal cut-off value of the HL motion ratio for the diagnosis of dysphagia was 0.58,leading to a sensitivity of 86.0%,a specificity of 93.0%and the area under curve of 0.967,respectively.Conclusion Ultrasonography can quantitatively evaluate the motion of the HL during swallowing,and the HL motion ratio can be considered as a parameter for the evaluation of stroke with dysphagia,providing new insights for clinical diagnosis of dysphagia.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective:To explore the metabolic outcomes of type 2 diabetes patients with different durations after 1 year treatment under the standardized metabolic disease management model.Methods:(1)From September 2017 to September 2018, 345 type 2 diabetes patients in the Standardized Metabolic Management Center(MMC) of Shanghai General Hospital were recruited and included in this research. They were divided into newly-diagnosed type 2 diabetes(duration≤1 year) and long-term groups(duration>1 year). The general characteristics, blood pressures, glycemic levels, lipids levels, control rates and comprehensive compliance rates(blood glucose, pressure and lipids all reached targets) were compared at baseline between 2 groups.(2)All patients underwent one year standardized management, and metabolic indicators mentioned above and control rates at the time were compared as well.Results:(1) At baseline, compared with long-term group, patients in newly-diagnosed type 2 diabetes group were younger ( P<0.01), and 2 h blood glucose level after glucose loading were higher [(15.20±5.26 vs 13.68±4.94) mmol/L, P<0.01]. (2) After one year standardized management, body weight, blood pressure, glucose and lipids metabolism in all patients were significantly improved. Compared with patients in long-term group, newly-diagnosed type 2 diabetes patients achieved better glycemic level [fasting blood glucose(6.27±1.56 vs 7.63±2.08) mmol/L, P<0.01; glycated hemoglobin(6.33±0.96 vs 7.23±1.37) %, P<0.01] , and had higher HOMA-β [(74.01±56.45 vs 40.17±37.07) %, P<0.01]. The glycemic control, blood pressure and blood lipids control rates in both groups increased significantly in one year. Comprehensive compliance rate of the whole patients increased from 5.80% to 24.06%. The metabolism indexes of the newly-diagnosed type 2 diabetes group were better than those of the long-term group[comprehensive compliance rate: (24.73% vs 17.18%, P=0.087, glycemic control rate(84.62% vs 53.37%, P<0.01)]. Conclusion:Standardized metabolic disease management promoted the overall improvement in blood glucose, blood pressure, and lipids levels in type 2 diabetes patients, especially in terms of blood glucose and those of the newly-diagnosed type 2 diabetes. In the future, we should focus on the early diagnosis and treatment of type 2 diabetes, actively promote the MMC model and stress the integrated management of blood glucose, blood pressure, and blood lipid levels. We should pay more attention to the long-term patients, to improve their awareness and treatment compliance.

Objective: To explore the glycemic control of newly-diagnosed type 2 diabetes with different levels of baseline body mass index (BMI) after 6 months treatment under the standardized metabolic disease management model. Methods: (1) 163 patients of newly-diagnosed type 2 diabetes were divided into normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI≥28 kg/m²) groups according to baseline BMI, the blood glucose and lipids levels were compared among 3 groups. (2) The blood glucose levels were compared among 3 groups after 6 months of standardized management. (3) The overweight and obese patients were divided into group weight loss≥5% and group weight loss<5% or weight gain in 6 months. The blood glucose levels were compared. Results: (1) At baseline, overweight and obese groups had higher homeostasis model assessment for insulin resistance and lower high density lipoprotein-cholesterol compared with normal weight group. (2) After 6 months of treatment, HbA_1C and HbA_1C reduction showed no difference among 3 groups (normal, overweight and obese) after adjusted by baseline HbA_1C. The rate of HbA_1C<7% among 3 groups were 77.78%, 83.95%, and 80.43% (P>0.05). (3) After 6 months of treatment, 32.28% overweight and obese patients lost weight by ≥ 5%, while HbA_1Cand HbA_1Creduction showed no difference between 2 groups (weight loss≥5% and weight gain or weight loss<5%) after adjusted by baseline HbA_1C. Both groups achieved good glycemic control [(6.27±1.38 vs 6.43±0.66)%], but have no significantly(P>0.05). Group weight loss≥5% had better glucose control (92.68% vs 77.91%, P<0.05). Conclusions As BMI increased, insulin resistance and lipid disorders were more serious in newly-diagnosed type 2 diabetes. After 6 months of standardized metabolic management, newly-diagnosed type 2 diabetes with different baseline BMI and weight changes both achieved good glycemic control. In addition, patients losing weight equal to or more than 5% achieved higher attainment of HbA_1C targets.