Objective:To evaluate the efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in the treatment of patients with initially unresectable hepatocellular carcinoma.Methods:The clinical data of 42 patients with initially unresectable hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were included. There were 31 males and 11 females, with a median age of 56 years old (range, 45-72 years old). All patients received TACE+ TKI+ PD-1 inhibitor combined treatment. The systemic treatment cycles were calculated by the regimen of immunotherapy. The timing of local treatment depends on tumor size, blood supply and treatment response. Patients were followed up through hospitalization, outpatient visits and telephone review. The Kaplan-Meier curves were obtained for survival analysis.Results:The dosing cycle to achieve optimal imaging response in the patients was 4 (3, 7) [ M( Q1, Q3)], with a systemic treatment time of 141 (65, 194) d [ M( Q1, Q3)] and 2 (1, 3) times [ M( Q1, Q3)] of local treatments. All patients were evaluated by modified response evaluation criteria in solid tumors criteria after treatment, including nine patients with complete response (CR), 21 with partial response, eight with stable disease, and four with progressive disease. Objective response rate and disease control rate were 71.4% (30/42) and 90.5% (38/42), respectively. Treatment-related adverse reactions occurred in 85.7% (36/42) of patients and grade Ⅲ or Ⅳ adverse reactions occurred in 16.7% (7/42). There was no level Ⅳ adverse reactions. All adverse reactions were controlled after dose reduction and symptomatic treatment. Thirteen patients (31.0%, 13/42) redeemed resectable after treatment and underwent radical surgery. Seven patients had pathological CR after surgery. In two patients, the pathological residual cancer tissue was less than 10%. The cumulative overall survival rates of the 42 patients at 6 months, 1 year, 1.5 years after treatment were 100%, 91.7%, and 65.0%, respectively. The postoperative 1-year survival rate of patients undergoing surgery after successful conversion was 83.3%. Conclusion:This study preliminarily showed the safety and efficacy of TACE, TKI, and PD-1 inhibitor combined therapy in patients with initially unresectable hepatocellular carcinoma.

Objective:To investigate the prevalence of hearing loss among community-dwelling older people aged 60 and over, and also to compare the discrepancies between self-reported hearing loss and hearing loss diagnosed via audiometry.Methods:Subjects were from the Prevention and Intervention on Neurodegenerative Disease for the Elderly in China(PINDEC)project.By using the stratified multi-stage cluster random sampling method, a total of 10 347 residents aged 60 years and over were selected from 12 counties and districts in Liaoning, Henan and Guangdong Provinces and hearing function assessment was performed in 2020 through otoscopy, pure-tone audiometry and questionnaires.Hearing loss(HL)was defined by the World Health Organization criteria.Self-reported hearing loss was assessed by asking participants whether they had difficulty in hearing.The χ2 and Cochran-Armitage trend tests were used to analyze the differences in HL between different groups.The multivariate Logistic regression model was applied to assess factors influencing HL. Results:In 2020, the prevalence of HL among the elderly aged 60 and older in Liaoning, Henan and Guangdong Provinces was 69.8%(95% CI: 68.9%-70.7%). The prevalence of HL in men was higher than that in women, and increased gradually with age.The prevalence of mild HL was 47.2%, and the prevalence of moderate, severe and profound HL were 18.0%, 3.6% and 0.9%, respectively.Multivariate Logistic regression analysis showed that factors positively correlated with HL were aging, male sex, living in rural areas and working in manual labor.Education level was negatively correlated with HL.Of the 7223 participants who were found to have HL, 5106(70.7%)self-reported having good hearing.Those of a younger age, with a higher educational achievement, having a spouse, or with mild HL were more likely to report having good hearing(all P<0.05). Conclusions:Hearing loss is quite prevalent among community-dwelling older people, and there is a large discrepancy in prevalence between self-reported HL and HL diagnosed via audiometry.Screening and comprehensive intervention for hearing loss for the elderly should be strengthened.

Abstract: To observe the histomorphological features of the hypothalamic-pituitary-adrenal axis in macaques to provide a reference for simulating the physiological functions and pathological responses of the human hypothalamic-pituitary-adrenal axis. Methods: After euthanasia of macaques, hypothalamus, pituitary and adrenal tissues were removed intact, fixed by PFA, and paraffin sections and frozen sections were prepared; the basic structure and cellular distribution were observed by HE staining; the secreted hormones and receptors were detected by immunohistochemistry; the effects of staining in frozen and paraffin sections were compared, and the cellular composition of some hypothalamus tissues was identified. Results: The hypothalamic region was hollow and funnel-shaped, the pituitary gland resembles a pea, and the right and left adrenal glands were located between the liver and kidneys; HE staining showed that the hypothalamic region was mainly composed of neurons and microglia, the pituitary gland was divided into neuro-pituitary and adeno-pituitary, and the adrenal gland was composed of cortex and medulla; immunohistochemical results showed that the hypothalamus secretes CRH and expresses GR, the pituitary gland secretes ACTH and expresses CRHR1 and GR, and the adrenal gland expresses ACTHR; immunofluorescence of frozen sections better showed that the hypothalamus contains neurons and microglia. Conclusion In this study, sections of hypothalamus, pituitary and adrenal gland tissues from macaques were successfully produced, and the relevant anatomical and morphological features were observed and examined, which provided a reference method for simulating the physiological and pathological responses of the human hypothalamic-pituitary-adrenal axis.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Objective To investigate effect of high dose irradiation on the performances of thermolumines-cence detectors (LiF:Mg, Cu, P). Methods The high-dose irradiated thermoluminescence detector was annealed by a thermoluminescence annealing furnace until the annealing was completed, and then the annealed thermoluminescent detector was irradiated 0.5Gy by 137Cs irradiator to verify the accuracy of the thermoluminescentdetector. Results The thermoluminescence detector after high-dose irradiation could not be completely annealed under the temperature condition of 240 ℃, and it could be completely annealed at a high temperature as 400℃. After 0.5 Gy irradiation by 137Cs irradiator, the measurement results of the annealed thermoluminescence detector were significantly smaller, and the dose response and dispersion of the detector were also changed significantly. Conclusions After a more than 5 Gy irradiation, the crystal structure of the thermoluminescence detector has changed, and a high temperature peak above 240 ℃ has appeared, which leads to the failure to completely anneal at normal temperature. Therefore, the thermoluminescence detector can no longer be used for dosimetry after high-dose irradiation.

Objective: To investigate the value of four-dimensional echocardiography combined with speckle tracking technique on the assessment of right heart function and prognosis in patients with pulmonary arterial hypertension (PAH). Methods: In this prospective study, 51 patients with PAH diagnosed by right heart catheterization in east hospital and south hospital of Renji hospital affiliated to school of medicine of Shanghai Jiaotong University from September 2015 to July 2017 were enrolled as PAH group from July to November 2017. Meanwhile, 26 healthy volunteers with age and sex matched with pulmonary hypertension patients were recruited as control group. The patients were aged (45.8±15.5) years old in PAH group, and there were 6 males and 45 females. The healthy volunteers were aged (45.4±14.6) years old in control group, and there were 4 males and 22 females. Two-dimensional and four-dimensional echocardiographic images were obtained to measure the structure and function of the right heart. The myocardial strain of each ventricle and atrium was measured by sparkle tracking. The patients in PAH group were followed up from July 2017 to August 2018 to observe the endpoint events including all-cause death, re-hospitalization, and clinical deterioration. Results: There were significant differences in two-dimensional echocardiographic parameters(including tricuspid annular plane systolic excursion (TAPSE), right ventricular area change fraction (FAC), and right ventricular systolic pressure (RVSP)), speckle tracking parameters (including global longitudinal systolic peak strain of left ventricle (LVGLS), global longitudinal systolic peak strain of right ventricle (RVGLS),left atrial reservoir function(LASr), left atrial conduit function (LASc), left atrial pump function (LASp), right atrial reservoir function (RASr), right atrial conduit function (RASc), and right atrial pump function (RASp)), and four-dimensional echocardiographic parameters(including right ventricular end diastolic volume (RVEDV) , right ventricular end systolic volume(RVESV), right ventricular stroke volume(RVSV), right ventricular freewall longitudinal strain(RVLSf), interventricular septum longitudinal strain(IVSLS), right ventricular ejection fraction(RVEF)) between control group and PAH group (all P<0.01 or 0.05).Spearman correlation analysis showed that RVEF was correlated with 6-minute walking distance (r=0.540, P<0.001), B-type natriuretic peptide (r=-0.545,P<0.001), New York Heart Association (NYHA) cardiac function classification(r=-0.583, P<0.001), TAPSE(r=0.595, P<0.001), LVGLS (r=-0.461, P=0.001) ,LASc (r=0.453, P=0.002) ,RASc (r=0.532, P<0.001) ,RVESV (r=-0.418, P=0.004) , RVSV (r=0.351, P=0.017) , and IVSLS (r=-0.450, P=0.002) . Pearson correlation analysis also showed that RVEF was correlated with FAC(r=0.579, P<0.001),RVSP (r=-0.442, P=0.002) ,RVGLS (r=-0.521, P<0.001) , LASr (r=0.483, P=0.001) , RASr (r=0.617, P<0.001) , RASp (r=0.513, P<0.001) , and RVLSf (r=-0.592, P<0.001) .After a follow-up of (10.4±2.7) months, there were 4 all-cause deaths, 5 re-hospitalizations and 5 clinical deterioration. Multivariate Cox regression analysis showed that increased RVEF was independent protective factor for end-point events in PAH patients (HR=0.702, P=0.043), and increased RVSP was independent risk factor for end-point events in PAH patients (HR=1.083, P=0.017). The receiver operating characteristic (ROC) curve showed that RVEF and RVSP could be used to predict the end-point events in PAH patients. The area under the curve (AUC) was 0.835(P=0.001) and 0.820(P=0.001), respectively. Conclusions RVEF measured by four-dimensional echocardiography is correlated with right ventricular function parameters measured by two-dimensional echocardiography and can be used to estimate the prognosis of PAH patients. The right atrial and left atrial function assessed by speckle tracking can also reflect the right ventricular function to a certain extent.

Objective To investigate the distribution of Helicobacter pylori (Hp) infections among general population in Tianjin. Methods Individuals (n=11 096) who visited our hospital for medical examination and H. Pylori infection screen were included in the research objects. Rapid urease method was utilized to rapidly detect H. pylori infection among the popultion. Individuals were grouped based on their gender, age and occupations, and then were analyzed. Results H. pylori-positive rate was 30.52%(3 386/11 096) in 11 096 individuals, in which there were 34.77%(1 784/5 131) male and 26.86%(1 602/5 965) female respectively. Individuals were divided into 5 groups according to their ages:19 to 29 years old group, 30 to 39 years old group, 40 to 49 years old group, 50 to 59 years old group, 60 to 69 years old group and 70 to 92 years old group. The positive rates of H. pylori increased with age:19.50%( 379/1 944 ) in 19-29 years old group, 25.82%(650/2 517 ) in 30-39 years old group, 31.59%( 908/2 874 ) in 40-49 years old group, 37.48%(915/2 441 ) in 50-59 years old group, 41.09%( 353/859 ) in 60-69 years old group and 39.18%(181/462) in 70-92 years old group. The differences in positive rates between different age groups were all of statistically significant (P<0.05). Individuals were also divided into seven groups according to their occupations: medical worker group, worker group, teacher group, engineer group, clerk group, civil worker group and other career group. The positive rates of H. pylori infection were 25.42%(586/2 305), 29.35%(1 062/3 618), 30.61%(360/1 176), 32.49%(116/357), 33.44%(205/613), 34.52%(455/1 318)and 35.23%(602/1 709) respectively. The positive rate was 25.42% (586/2 305) medical workers, which was lower than that of other occupation groups with significant difference (P<0.002). Conclusion Good management of H. pylori diagnosis and treatment in mid-dle age and elderly together with popularizing knowledge of H.pylori prevention can effectively reduce H.pylori incidence.

Objective To study the relationship between the clinic-pathological features and pain symptoms in patients with endometriotic cyst(EM).Methods The medical data of symptoms,laparoscopy and pathology examination in 416 patients with endometriosis were studied retrospectively.All cases were divided into two groups on the existence of ovarian endometrioma,including 338 patients in cyst group and 78 cases in non-cyst group.The relationship between clinical symptoms and location and type of endometrioma was studied.Results(1)Serum CA125 level:the level of CA125 were(61 ± 39)kU/L in cyst group(28 ± 24)kU/L in non-cyst group,which reached statistical difference(P ＜ 0.01).(2)Pathological features:among 338 cases,34.0％ of cyst were on left side(115/338),26.3％ were right side(89/338),and 39.6％ were on both side(134/338).And 95.8％(324/338)of cases were combined with the other type of endometriosis,which were 48.5％(164/338)with peritoneal endometriosis,47.3％(160/338)with deep infiltrating endometriosis(DIE).In cystic patients,the incidences of endometriosis lesion were 13.9％(47/338)on the uterine surface,38.5％(130/338)on obstruction of cul-de sac,40.5％ (137/338)on utero-sacral ligament of DIE,which were significantly higher than 5.1％,(4/78),9.0％ (7/78)and 28.2％(22/78)in noncyst group.(3)Pain symptom:the incidence and degree of dysmenorrhea and dyschezia had no statistical difference between two groups(P ＞ 0.05),and the incidence of chronic pelvic pain(CPP)of 24.6％(83/338)and dyspareunia of 29.9％(101/338)in the cyst group were significantly lower than 35.9％(28/78)and 44.9％(35/78)in non-cyst group(P ＜ 0.05).The incidence of dysmenorrheal was 85.1％(114/134)in cases with bilateral cyst,which was higher than 74.0％(151/204)in cases with single cyst.The incidence of dysmenorrheal and dyschezia in moderatesevere adhesion was 89.0％(138/155)and 18.7％(29/155),which was significantly higher than 68.8％ (126/183)and 8.2％(15/183)in mild adhesion.In the patients cyst existed with DIE,the risk of dysmenorrheal,CPP,dyspareunia,and dyschezia were obviously raised(OR respectively was 5.17,3.01,3.05,2.75).Conclusions The endometriotic cyst often co-exists with other type of endometriotic lesions.Ovarian endometrioma was associated with lesion localized on uterine surface,cul-de-sac,sacrum ligament.The risk of all the pain symptoms would be raised when the endometriotic cyst co-exit with the DIE lesions.So the treatment for DIE lesions was as same important as the endometriotic lesions in order to relieve pain symptoms and delay the relapse.

ObjectiveTo investigate the characteristics of left ventricular structural damage in patients with primary aldosteronism(PA).MethodsA total of 438 inpatients with hypertension from January 2007 to June 2010 were screened for PA,and diagnosis was made in 213 PA patients and 225 patients with essential hypertension (EH).The left ventricular structure of all subjects was evaluated according to the results of echocardiographic measurements.Results The duration of hypertension and plasma aldosterone level in patients with PA were significantly higher (P＜ 0.01 ),while the serum potassium and plasma renin activity were significantly lower (P＜0.01 ) than those in patients with EH.The interventricular septum thickness,left ventricular end-diastolic dimension,left ventricular mass index (LVMI),left ventricular end-diastolic volume,and stroke volume in patients with PA were significantly higher than those in EH patients( P＜0.01 ) after the duration of hypertension was corrected.In patients with PA,the prevalence of left ventricular hypertrophy (LVH) was higher than that in EH patients ( 53.1％ vs 33.8 ％,x2 =16.57,P ＜ 0.01 ). Normal left ventricular geometry ( NG ),concentric remodeling ( CCR ),concentric hypertrophy( CCH),and eccentric hypertrophy (ECH) were found respectively in 24.9％,22.1％,22.1％,and 30.9％ of patients with PA.Multiple stepwise regression analysis showed that the seated plasma aldosterone level (β=0.43,P ＜ 0.01 ) and systolic blood pressure (β =0.45,P ＜ 0.01 ) were the main factors that influenced LVMI.The course was the main parameter that influenced relative wall thickness(β=0.011,P＜0.05 ).Conclusion The prevalence of LVH is higher in patients with PA than that in EH patients.The eccentric hypertrophy is the most common left ventricular geometrical pattern in patients with PA.