[Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years].

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly.

PURPOSE: Acromegaly caused by growth hormone cell adenoma is commonly associated with abnormal glucolipid metabolism, which may result from changes in adipocytokine secretion. This study aims to investigate serum adipokine levels, including pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG), in acromegalic patients and the correlation between the levels of these three adipokines and GH levels and glucolipid metabolism indices. METHODS: Sixty-eight acromegalic patients and 121 controls were included, and their clinical data were recorded from electronic medical record system. Serum PNT, furin and ZAG levels were measured by ELISA. RESULTS: Serum PNT levels in acromegalic patients were significantly higher than controls (66.60 ± 12.36 vs. 46.68 ± 20.54 pg/ml, P < 0.001), and acromegaly was an independent influencing factor of PNT levels (P < 0.001). Moreover, subjects with the highest tertile of PNT levels had a close correlation with acromegaly (OR = 22.200, 95% CI 7.156 ~ 68.875, P < 0.001), even in Model 1 adjusted for gender and age and Model 2 adjusted for gender, age and BMI. Additionally, serum PNT levels were positively correlated with BMI (r = 0.220, P = 0.002) and triglycerides (TGs, r = 0.295, P < 0.001), and TGs were an independent influencing factor of serum PNT levels in acromegalic subjects (P < 0.001). Furthermore, serum PNT levels in obese acromegalic patients were significantly higher than those with normal BMI (P < 0.05). However, serum furin levels were lower in acromegalic patients than controls (0.184 ± 0.036 vs. 0.204 ± 0.061 ng/ml, P < 0.001). CONCLUSION: This study is the first to demonstrate that acromegalic patients have increased serum PNT levels. Moreover, serum PNT plays a potential role in abnormal lipid metabolism of acromegalic patients.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

[Rethinking of the conversion therapy in colorectal cancer patients with liver metastasis].

The incidence of colorectal cancer liver metastasis (CRLM) has gradually increased in recent years. Surgical resection is the main method to achieve long-term survival for patients with CRLM. However, only 20% of these patients have the chance to undergo surgical resection. If the unresectable metastases can be converted to resectable ones by effective conversion therapy, the 5-year survival rate of patients received liver resection can exceed to 30%, which is significantly better than palliative treatment. Therefore, for patients who are initially unresectable, rationally developing a conversion therapy strategy to convert the initial unresectable CRLM into resectable ones is the key to improve the long-term survival of CRLM patients. However, there are still many controversies in clinical practice. In this article, we discuss three critical issues related to the conversion therapy for CRLM based on previous related researches and our experience, including the applicable population of conversion therapy, how to choose a conversion regime and the recognition and treatment of disappeared lesions after chemotherapy.

[The correlation of ganglion cell layer thickness with visual field defect in non-functional pituitary adenoma with chiasm compression].

Objective: To investigate the consequences of the thickness of ganglion cell layer (GCL) and visual field defect of non-functional pituitary adenoma with chiasm compression. Methods: A case control study. The study included 40 (80 eyes) non-functional pituitary adenoma patients in Peking Union Medical College Hospital from March 2015 to February 2017. Twenty patients (no visual field defect group, 40 eyes) of them were detected to be chiasm compressed or touched by the adenoma with no visual field defect detected, and the other 20 patients (visual field defect group, 40 eyes) were the sex-and-age matched pituitary adenoma patients with bitemporal heminopsia. This study also included 20 (control group, 40 eyes) sex-and-age matched healthy controls. The para-papillary retinal nerve fiber layer (RNFL) thickness in 6 quadrants including nasal, temporal, nasal superior, temporal superior, nasal inferior and temporal inferior as well as the macular GCL thickness and ganglion cell-inner plexiform layer (GCIPL) thickness in 4 quadrants including nasal superior, nasal inferior, temporal superior and temporal inferior were measured. The non-parametric test was used to compare the RNFL, GCL and GCIPL thickness among the three groups. Results: The mean age among the three groups was (46±10) years and the difference among the three groups was not significant (P=0.88). The sex ratio of the three groups was 9∶11 (male∶female) and the difference among the three groups was not significant. The mean axial length among the three groups was (23.22±0.90) mm and the difference among the three groups was not significant (P=0.51). The thickness of para-papillary RNFL of temporal superior, temporal, nasal superior, nasal, nasal inferior quadrants and whole circumference was significantly thinner in the visual field defect group than the control group [(129.88±28.64) µm, (63.63±26.84) µm, (88.08±32.16) µm, (50.68±19.99) µm, (92.48±25.06) µm, and (85.00±20.65) µm vs. (141.10±18.95) µm, (79.12±16.78) µm, (113.68±21.28) µm, (69.67±14.23) µm, (117.80±31.32) µm, and (102.80±9.68) µm, t=2.26, 3.06, 4.14, 4.84, 4.25, 4.88, all P<0.05]. In the nasal quadrant, the para-papillary RNFL of the no visual field defect group was significantly thinner compared with the control group [(61.45±9.83) µm vs. (69.67±14.23) µm, t=2.97, P<0.05]. The total GCL thickness was (30.48±5.42) µm in the visual field defect group, (31.35±2.77) µm in the no visual field defect group, thinner than that in the control group [(33.32±2.92) µm, t=2.92, 3.62; both P<0.05]. The total GCIPL thickness showed no significant difference among the three groups (P=0.07). In the superior and inferior temporal quadrants, the GCL and GCIPL thickness showed no significant difference among the three groups (all P>0.05). In the superior and inferior nasal quadrants, the GCL thickness was (29.41±5.97) µm, and (28.47±5.13) µm in the visual field defect group, (31.15±3.27) µm and (30.61±2.96) µm in the no visual field defect group, and (34.23±3.16) µm and (32.97±2.78) µm in the control group. The GCL thickness in the nasal quadrant was thinner in the visual field defect group (t=4.45, 4.82)and the no visual field defect group(t=4.23, 3.63) than in the control group (all P<0.01). However, no significant difference in GCL thickness was detected between the visual field defect group and the no visual field defect group (both P>0.05). In the superior and inferior nasal quadrants, the GCIPL thickness was (54.06±10.50) µm and (51.77±9.18) µm in the visual field defect group, (58.03±4.00) µm and (56.23±5.37) µm in the no visual field defect group, and (62.26±7.11) µm and (59.39±6.64) µm in the control group. The GCIPL thickness was thinner in the nasal quadrant in the visual field defect group than in the control group (t=3.95, 4.20, both P<0.01). Only in the Superior nasal quadrant, the GCIPL was significantly thinner in the no visual field defect group than the control group (t=3.25, P<0.01). Conclusion: The optic GCL may get thinner in pituitary nonfunctional adenoma with chiasm compression patients without the RNFL layer thinning and visual field defect. (Chin J Ophthalmol, 2019, 55: 186-194).

[A retrospective study of the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China in 2013-2014].

Objective: To study the inducing factors and clinical characteristics of patients hospitalized for asthma exacerbation in China. Methods: Patients hospitalized for asthma exacerbation at 29 hospitals in China were retrospectively recruited during 2013-2014. Results: Clinical data of 3 240 asthmatic patients were collected and analyzed including 1 369(42.3%) males and 1 871(57.7%) females. The patients hospitalized for asthma exacerbation counted for 2.95% (6 375/215 955) of all patients hospitalized during the same period. The leading six inducing factors, in sequence, were acute upper respiratory tract infection [42.3%(1 370/3 240)], changes of weather [22.8%(738/3 240)], noxious gas [(4.3%(140/3 240), allergy challenges [3.5%(115/3 240)], strenuous exercise [1.8%(57/3 240)], and air pollution [1.5%(49/3 240)]. In older patients, more exacerbations were induced by weather changes, yet less sensitive to allergy challenges. As to middle-aged patients, they were less sensitive to upper respiratory tract infections, however the difference was not statistically significant (P>0.05). In winter more asthma patients were induced by upper respiratory tract infections, while in autumn more patients were induced by weather changes, strenuous exercise and air pollution. In spring and summer more patients were induced by allergy challenges, but the differences failed to achieve statistical significance (P>0.05). In northern cities more patients were induced by upper respiratory infections, whereas in southern cities more by noxious gases. Allergy challenges and air pollution tended to affect more patients in northern cities, but the difference was of no significance (P>0.05). The differences of inducing factors among patients of different gender, with or without a smoking history, and with different exacerbation severity didn't show any statistical significance. The patients with severe and life-threatening exacerbations counted for 20.1% (652/3 240). The percentage of patients older than 60 years was higher in patients with severe or life-threatening exacerbations than in whose with mild or moderate exacerbations, so did the percentage of male patients, of patients with disease duration longer than 10 years, with smoking history, and with a history of hospitalization or emergency department visits due to asthma exacerbation during the last year. Conclusion: The acute upper respiratory tract infection ranks top among all the inducing factors. Senility, male gender, long duration of disease, smoking history, and a history of frequent hospital visits might be the risk factors for severe or life-threatening asthma exacerbations.

[Correlation between the parameters of acoustic cardiography and BNP, LVEF and cardiac function grading in patients with chronic heart failure].

Objective: To explore the correlation between the parameters of the new generation of Acoustic Cardiography and brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and cardiac function grading in the diagnosis of heart failure. Methods: One hundred and sixty-eight inpatients, who were hospitalized in Department of Cardiology, Haikou People's Hospital from May 2016 to July 2017, were enrolled as heart failure group, including NYHA class Ⅰ(n=29), NYHA class Ⅱ(n=40), NYHA class Ⅲ(n=64), NYHA class Ⅳ (n=35). And eighty-seven patients with normal cardiac function were selected as healthy control group. The data of the two groups were analyzed after the Acoustic Cardiography test, BNP determination and LVEF examination. Results: The differences in QRS duration, electromechanical activation time (EMAT), EMAT%, systolic dysfunction index (SDI), third heart sound (S3) and other indicators among the groups with different levels of cardiac function were statistically significant (P<0.05). The difference in left ventricular systolic time (LVST) between the cardiac function grade Ⅰ and healthy group was not significant (P>0.05), while the differences among the rest groups were significant. There was a positive correlation between QRS duration, EMAT%, SDI, S3 and BNP (t=9.46, 11.38, 12.14, 9.67, respectively, P<0.05); LVST and BNP were negatively correlated (t=-14.27, P<0.05). There was a negative correlation between QRS duration, EMAT%, SDI, S3 and LVEF (t=11.24, -8.764, -2.393, -0.579, respectively, P<0.05). There was a positive correlation between LVST and LVEF (t=23.48, P<0.05). There was a positive correlation between QRS duration, EMAT%, SDI, S3 and cardiac function grading (ß=0.003, 0.234, 0.419, 0.352, respectively, P<0.05). There was a negative correlation between LVST and cardiac function grade (ß=-0.021, P<0.05). Conclusion: The parameters of the Acoustic Cardiography test (EMAT%, EMAT, SDI, S3 ) are closely related to BNP, LVEF and cardiac function grading, and can be used as assistant indexes for the diagnosis and evaluation of heart failure.

[Effect of long-term asthma management on asthma patients from China-Japan Friendship Hospital].

Objective: To investigate the outcome of long-term asthma management of China-Japan Friendship Hospital. Methods: A face-to-face, questionnaire-based survey was carried out in outpatient department in 30 general hospital (including China-Japan Friendship Hospital) from Oct 2015 to May 2016. Data of demographic characteristics, asthma control, asthma management, asthma attacks and self-management, disease perception was collected. Results from China-Japan Friendship Hospital were compared to the national mean level within the same period. Results: Altogether 150 asthmatic outpatients were recruited from China-Japan Friendship Hospital. Asthma control level was significantly higher than the national asthma control level[56.7% (85/150) vs 28.5% (1 099/3 854), P<0.001]. The rate of hospitalizations due to asthma exacerbations was significantly lower than the national hospitalization rate[13.3% (20/150) vs 26.4% (1 017/3 858), P<0.001]. The rate of peak flow meter (PFM) usage was significantly higher than the national PFM usage rate[50.7% (76/150) vs 10.1% (388/3 837), P<0.001]. For reasons of not using PFM, the proportion of doctors never introduced was lower than the national level[43.3% (65/150) vs 65.2% (2 518/3 860), P<0.001]. As to the choice of anti-asthmatics when symptoms deteriorated, the proportion of inhaled corticosteroid (ICS)+ formoterol was significantly higher than the national level[70.0% (105/150) vs 45.8% (1 776/3 875), P<0.001]. The proportion of the patients that had right perception on disease nature was significantly higher than the national level[78.7% (118/150) vs 69.0% (2 660/3 857), P=0.011]. The proportion of the patients that had right perception on medication choice on daily-used first-line medication for chronic asthma was significantly higher than the national level[70.7% (106/150) vs 60.2% (2 321/3 857), P=0.010]. Conclusion: The level of asthma control, disease management and disease perception in China-Japan Friendship Hospital are much higher than national level due to the conduction of long-term asthma management.

[A retrospective study of the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas].

Objective: To study the mortality and death-related risk factors of patients hospitalized for asthma exacerbation in Chinese urban areas. Methods: A retrospective study was carried out in 29 hospitals of 29 provinces throughout mainland China. Patients hospitalized for asthma exacerbation during 2013-2014 in each hospital were included. For each patient, information about demography, admission time, comorbidities, severity of diseases, intense care unit (ICU) admission, use of mechanical ventilation and the outcome was obtained. The mortality of patients hospitalized for asthma exacerbation was calculated, and the basic information and causes of death of the patients who died were summarized. The death-related risk factors and numbers of comorbidities were compared between the patients who survived and those who died during hospitalization. Results: A total of 3 240 patients (median age 57.0) were included and among them 8 patients (median age 68.5) died. The mortality of patients hospitalized for asthma exacerbation was 0.25%. All the patients who died were admitted during the winter and spring. One patient died of acute myocardial infarction, one of cardiac shock, one of tension pneumothorax, one of sudden death, one of respiratory failure and three of unknown causes. The average number of comorbidities of patients who died was 1.10, larger than that of patients who survived (0.83) (P>0.05). More patients had diabetes, coronary artery diseases and hypertension as comorbidities in the patients who died (2/8) than those who survived[7.6% (246/3 232), 7.6% (246/3 232), 22.6% (731/3 232), respectively](all P>0.05). Conclusions: The in-hospital mortality of patients hospitalized for asthma exacerbation of China in this study is low. The patients who died are much older, and with more comorbidities, and a higher percentage of comorbidities such as diabetes, coronary artery diseases, and hypertension.

[A retrospective study of the treatment of patients hospitalized for asthma exacerbation in China].

Objective: To study the treatment of patients hospitalized for asthma exacerbation in China. Methods: This was a retrospective study and involved patients hospitalized for asthma exacerbation in 29 hospitals throughout China during Jan 2013 to Dec 2014. Information of the demographic features, the severity of the exacerbation, the medicine prescribed during the hospitalization and the use of mechanical ventilation were collected and analyzed. Results: During the study period, there were 3 240 patients hospitalized for asthma exacerbation, and 1 369(42.3%) of them were males 1 871(57.7%)were females. Patients of mild, moderate, severe, and life-threatening exacerbation counted for 41.7%, 37.8%, 19.2% and 1.0%, respectively of the total patients. Of all the patients, 72.6% used bronchodilators by nebulizer, 70.8% used inhaled corticosteroids by nebulizer, 60.5% used intravenous corticosteroids, 17.3% used oral corticosteroids, and 80.5% used antibiotics. The percentages of patients using systemic corticosteroids and antibiotics were higher in patients with more severe exacerbation. In patients with mild exacerbation, there were 74.9% and 52.2% who used antibiotics and systemic corticosteroids, respectively. A total of 73 patients (2.3%) used mechanical ventilation, and 62 of them used noninvasive ventilation, 16 used invasive ventilation, and 5 used both. Conclusions: Nebulizer therapy has been accepted as the main administration route of medicine in the treatment of asthma exacerbation. A large amount of patients used antibiotics and systemic corticosteroids during hospitalization, indicating there may be some overuse of these medicines.

The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study.

OBJECTIVE: A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis (OA) of the hand in European populations. However, these findings have not been well generalized to other joints, or to other populations. METHODS: We performed a two-stage population-based case-control study including 196 non-post traumatic knee OA cases and 442 controls in the first stage and independent 143 non-post traumatic knee OA cases and 238 controls in the second stage in a Chinese population by genotyping eight tagging polymorphisms in ALDH1A2. RESULTS: In the first stage, the single nucleotide polymorphism (SNP) rs4238326 was found to be potentially associated with knee OA risk (additive model: odds ratio [OR] = 0.70; 95% confidence interval [95% CI] = 0.49-1.01; P = 0.055), which was further confirmed in the second stage with similar effect (additive model: OR = 0.60; 95% CI = 0.38-0.95; P = 0.029). After combining the two stages, we found that the variant C allele of rs4238326 was probably associated with decreased risk of knee OA (additive model: OR = 0.65; 95% CI = 0.49-0.86; P = 0.003). Furthermore, interaction analyses showed that rs4238326 interacted multiplicatively with age to contribute to knee OA risk (interaction P = 0.041). CONCLUSIONS: These findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Chinese population. Beyond that, further studies are warranted to validate and extend our findings, and future functional studies are required to clarify the possible mechanisms.

Analysis of bromocriptine treatment in pregnant pituitary prolactinoma patients.

OBJECTIVE: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma. MATERIALS AND METHODS: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine. RESULTS: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05). CONCLUSION: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

[Seasonal characteristics of patients hospitalized for asthma exacerbation in China].

Objective: To study the seasonal characteristics of patients hospitalized for asthma exacerbation in China. Methods: This was a retrospective study which involved patients hospitalized for asthma exacerbation in 29 hospitals throughout mainland China during 2013-2014. The number of patients hospitalized for asthma exacerbation in each hospital was calculated, as well as the ratio of asthmatic patients to all the hospitalized patients. The analysis by month was conducted. The number and ratio of asthmatic patients in the northern and southern cities were calculated respectively. Results: During the study period, there were 6 480 patients hospitalized for asthma exacerbation, accounting for 3.14% (6 480/206 135) of all the hospitalized patients of the respiratory department in 29 hospitals. The analysis by month showed that the ratio of patients hospitalized for asthma exacerbation was highest in March (3.49%), then declined from April to June, then rose again from July, reaching a second peak at September (3.28%), and then declined again from October to December. The ratio of asthmatic patients in every month was higher in northern cities than in southern cities. Conclusions: The ratio of patients hospitalized for asthma exacerbation in China fluctuates with the changes of seasons, and March and September are the two peak months. Northern cities have a higher ratio of asthmatic patients than southern cities.

[Association between A-kinase anchor proteins 12 methylation and recurrence of hepatocellular carcinoma].

Objective: To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years. By the end of May 2014, a total of 75 patients had relapsed of whom 71 died and there were no lost. All samples were acquired from the frozen surgical tissues. Genomic DNA was extracted using phenol/chloroform method and performed bisulfite modification following with polymerase chain reaction (PCR). AKAP12 methylation in hepatoma and the corresponding SM samples from 142 patients was determined by denature high-performance liquid chromatography (DHPLC) and bisulfite clone sequencing. Kaplan-Meier and Cox proportion hazard regression model were used to identify the factors related to the survival time. Results: In 142 cases, 125 patients (88.0%) were male and 17 (12.0%) cases were female. The median age was 52.5 years, ranging from 34 years to 76 years. AKAP12 methylation-positive rate was significantly higher in hepatomas than SMs (54.9% vs. 10.2%, P<0.001). Patients with AKAP12 methylation-positive had less risk of the recurrence (HR=0.62, 95%CI: 0.39-0.99); with tumor diameter more than 5 cm (HR=1.53, 95%CI: 1.00-2.50),portal vein invasion(HR=4.53, 95% CI:2.69-7.64) increased the recurrence risk. Moreover, portal vein invasion had a higher risk of death (HR=2.98, 95% CI: 1.73-4.98). Conclusion: There was significant association between AKAP12 DNA methylation and low risk of recurrence and long progression-free survival of hepatocellular carcinoma patients.

[A multi-center retrospective study of clinical characteristics and hospitalization costs of patients hospitalized for asthma exacerbation in China during 2013-2014].

Objective: To study the characteristics of patients hospitalized for asthma exacerbation in 29 teaching hospitals in China and to evaluate the hospitalization costs of these patients. Methods: This was a retrospective study and involved patients hospitalized for asthma exacerbation in 29 hospitals throughout China during 2013-2014. Information about the demographic features, conditions before the admission, the outcome, the complications, and the costs was collected using the pre-designed case report form. The influencing factors of the hospitalization costs were analyzed. Results: 3 240 asthmatic patients (1 369 males and 1 871 females) were included and data were analyzed. There were 41.5% (1 346/3 240) patients who had a history of previous hospitalization or emergency department visits during the last year. Only 28.0% (907/3 240) patients had used asthma-controlling medications regularly before the admission. Seventy-three(2.3%) patients were admitted to ICU and used mechanical ventilation. Mortality among these patients hospitalized for asthma exacerbation was 0.25% (8/3 240). The median hospitalization costs was 9 045(6 431, 13 035) RMB. The costs of medications, examinations and treatment accounted for 52.1%, 27.6%, and 9.6% respectively. The costs of asthma medications accounted for only 22.7% of the total medication costs, while the costs of antibiotics accounted for 44.0%. The patients who were admitted to ICU, used mechanical ventilation, complicated with pneumonia, or had a history of hospitalization or emergency department visits during the last year due to asthma exacerbations tended to cost more. Conclusion: In this study, we demonstrated that only a minority of the patients had used asthma controllers regularly before the admissions with exacerbations. The in-hospital mortality of asthma patients in this study was much lower than that reported in other countries. The average cost of hospitalization was much higher than the yearly cost of maintenance therapy. Medication was the predominant component of the total hospitalization costs, and the costs of antibiotics made up the major part of the total medication costs.

[The surgery of thyrotropin-secreting pituitary adenomas and the significance of thyroid stimulating hormone level in follow-up].

Objective: To explore the clinical characteristics of thyrotropin-secreting pituitary adenomas and the effect of the transsphenoidal approach of procedure with/without drug treatment for thyrotropin-secreting pituitary adenomas, and to investigate the correlation between the prognosis of thyrotropin-secreting pituitary adenomas and the postoperative level of thyroid stimulating hormone (TSH). Methods: A total of 45 patients with thyrotropin-secreting pituitary adenoma who hospitalized in Peking Union Medical College Hospital from 2000 to 2015 were enrolled in the study.We collected the clinical features, hormone levels, imaging findings, treatment and follow-up data of these patients. Results: The average age of the patients was 40.26 years old and the average disease duration was 5.83 years.Among them, 8 cases were microadenomas and 37 cases were macroadenoma.Thirty patients were treated with somatostatin analogues before surgery.TSH level was significantly decreased after operation (P=0.012). All of them had done the pituitary surgery, including 44 transsphenoidal surgery and 1 subfrontal surgery that had recurrence one year after the transsphenoidal surgery.The TSH level of 34 cases went back to normal on the third day after surgery.The remission rates on three months and one year after surgery in patients with TSH level<0.1 mIU/L on postoperative day (POD) 3 were significantly higher than those in patients with TSH level>0.1 mIU/L on POD3.As well as the remission rates on three months and one year after surgery in patients with TSH level normal on postoperative one month were significantly higher than those in patients with TSH level abnormal on postoperative one month. Conclusions: TSH level of postoperative one month could be used to predict prognosis and monitor recurrence.

[Analysis of curative effect of surgical therapy for male prolactinoma].

OBJECTIVE: To summarize the treatment outcome of surgery for male prolactinoma. METHODS: One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach. RESULTS: Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index≤3 (P<0.01). CONCLUSION: Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index.

[Surgical treatment of pituitary adenomas in childhood and adolescence].

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.

[Analysis of outcomes and learning curve of endoscopic transsphenoidal surgeries for 124 patients with pituitary adenomas].

OBJECTIVE: To investigate the outcomes of the Endoscopic transsphenoidal surgery for patients with pituitary adenomas, analyze the learning curve and provide reference for future surgeries. METHODS: Retrospective analysis was carried out on 124 patients by endoscopic transsphenoidal surgery with a single neurosurgeon over a period spanning from January 2010 to January 2014 at Peking Union Medical College Hospital.The changes of endocrine and tumor imaging before and after surgery were analysed. Operative time and complication rates of one surgeon in the early period of learning curve were compared with that in later period. RESULTS: There were significant differences in Gross total resection (GTR) rate of pituitary adenomas with different sizes and different Knosp classifications (P<0.01, P<0.01). GTR rate of huge adenomas was significantly lower than that of macroadenoma and adenomas (P<0.05). GTR rate of Knosp 4 grade adenoma was significantly lower than that of Knosp 0-3 level (P<0.05). No significant difference in GTR among all types of functional pituitary adenomas and hormone levels after surgery was observed (P>0.05). In addition, no significant difference (P>0.05) in complications among different sizes, Knosp grade and type of pituitary adenomas was observed.GTR of Knosp 4 adenoma in later period of the learning curve was significantly higher than that in early period (P<0.05). Meanwhile the operative time was significantly lower than early period (P<0.05). CONCLUSIONS: Endoscopic transsphenoidal pituitary adenoma resection has the advantages of wider surgical field, higher GTR rate, less trauma, fewer complications and better life quality of patients.Through standardized learning, the GTR rate of the invasive pituitary adenomas can be improved.