OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.
Humans ; Laser Therapy ; Male ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms ; Risk ; Watchful Waiting

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

BACKGROUND: Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied. METHODS: We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups. RESULTS: Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13-0.76, χ2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13-1.43, χ2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53-2.69, χ2 = 0.17, P = 0.6777). CONCLUSIONS In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; COVID-19 ; Calcium Channel Blockers/therapeutic use* ; Child ; China ; Humans ; Hypertension/drug therapy* ; Prognosis ; Retrospective Studies ; SARS-CoV-2

Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN.

Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups.

The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression.

Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.

Objective To investigate the dynamic changes and prognosis of thyroid function in the patients with chronic hepatitis C (CHC)after antiviral treatment,and to clarify the influence of baseline factors in the changes of thyroid function.Methods 243 CHC patients with normal baseline thyroid function were enrolled. All patients were treated with IFN-alpha-2b(IFN-α2b)combined with ribavirin for 48 weeks.The thyroid function and serum HCV RNA level were assessed at 12,24,36,48,60 and 72 weeks.According to the changes in thyroid function after treatment,the patients were divided into continued normal,subclinical hypothyroidism,hypothyroidism and hyperthyroidism groups.The regularity of the changes of thyroid function of the patients in various groups were observed.Results Among 243 CHC patients,82(33.7%)patients had thyroid dysfunction.The prevalence of subclinical hypothyroidism,hypothyroidism and hyperthyroidism were 20.9%(51/243),5.3%(13/243)and 7.4%(18/243),respectively. At the end of 72 weeks,there were 32 (39.0%)patients suffering from subclinical hypothyroidism,12 (14.6%) patients with hypothyroidism and 7 (8.5%) patients with hyperthyroidism rehabilitated.6(7.3%)patients suffering from hypothyroidism turned to subclinical hypothyroidism,and 3(3.7%) patients suffering from hyperthyroidism turned to subclinical hypothyroidism.19(23.2%)patients had no significant change,they performed for continued subclinical hypothyroidism (1,1.2%),hypothyroidism (13,15.9%)and hyperthyroidism (5 , 6.1%).In addition, 3 (3.7%)patients with hyperthyroidism turned to hypothyroidism.An increased risk for hypothyroidism was found in female patients compared with males (P<0.05);the average age of the patients with hyperthyroidism was lower than those of the patients with hypothyroidism, subclinical hypothyroidism and continued normal (P<0.05);the baseline levels of GGT in the patients with hyperthyroidism and hypothyroidism were lower than those of the patients with subclinical hypothyroidism and continued normal(P<0.05).The ratio of the patients with HCV 2a to the patients with hypertyroidism was higher than those of the patients with hypothyroidism,subclinical hypothyroidism and continued normal(P<0.05).Conclusion Thyroid function in the CHC patients can be affected by antiviral treatment. Gender, age, liver function, genotype of HCV are influencing factors for the changes of thyroid function.

Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.
Adjuvants, Immunologic ; Animals ; Bacterial Proteins ; genetics ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Ehrlich Tumor ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Diphtheria Toxin ; genetics ; immunology ; Female ; HSP70 Heat-Shock Proteins ; genetics ; immunology ; Immunoglobulin G ; immunology ; Immunotherapy ; Mice ; Neovascularization, Pathologic ; Peptide Fragments ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tandem Repeat Sequences

BACKGROUNDHepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. In order to investigate the molecular biologic mechanism of HCC's development, we studied the expressions of SE-1, CD105 and CD31 in tumor endothelial cells (TECs) of HCC and in the serum of rats.

METHODSWe analyzed the expressions of SE-1, CD31 and CD105 in rat HCC tumor tissues using immunohistochemistry (IHC). Twenty HCC bearing rats and eighteen normal rats were examined for the expressions of SE-1, CD31 and CD105 antigens in serum by enzyme-linked immunosorbent assay (ELISA).

RESULTSSE-1, CD31 and CD105 antigens were detected both in HCC tissue and in normal liver tissue with higher expressions of CD31 and CD105 in HCC while the SE-1 antigen expression was higher in normal liver. Similarly, serum CD31 and CD105 in rats with HCC were significantly increased compared with normal rats (t = 2.8628, P = 0.0086; t = 4.4922, P < 0.0001, respectively). In contrast, SE-1 antigen in HCC rat serum was significantly decreased compared with normal rats (t = 3.4983, P = 0.0011).

CONCLUSIONSE-1, CD31 and CD105 are closely related with liver tumor angiogenesis, which is similar to their performances in terms of their expressions in the serum.

Animals ; Antigens, CD ; blood ; Carcinoma, Hepatocellular ; blood supply ; chemistry ; Endothelial Cells ; chemistry ; immunology ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; Liver Neoplasms, Experimental ; blood supply ; chemistry ; Male ; Neovascularization, Pathologic ; blood ; Platelet Endothelial Cell Adhesion Molecule-1 ; blood ; Rats ; Rats, Inbred BUF

BACKGROUNDThe clinical outcome of percutaneous coronary intervention (PCI) is poorer in women than that in men. This study aimed at comparing the impact of gender difference on the strategy of primary PCI in patients with acute ST-segment elevation myocardial infarction (STEMI).

METHODSTwo hundred and fifty-nine patients with STEMI who underwent primary PCI within 12 hours of symptom onset were enrolled. The male group consisted of 143 men aged > 55 years, and a female group included 116 women without age limitation. Procedural success was defined as residual stenosis < 20% with thrombolysis in myocardial infarction flow grade > 2 and without death, emergency bypass surgery or disabling cerebral events during the hospitalization. The rate of major adverse cardiac events (MACE), including death, nonfatal myocardial infarction and target vessel revascularization during follow-up, was recorded.

RESULTSFemale patients were more hypertensive and diabetic and with fewer cigarette smokers than male counterparts. The prevalence of angiographic 3-vessel disease was higher in the female group, but the procedural success rate was comparable between the two groups (94.4% vs 92.2%). The occurrence rate of MACE did not differ during the hospitalization (4.2% vs 6.0%, P = 0.50), but was significantly higher in the female group during follow-up (mean (16.0 +/- 11.2) months) than that in the male group (5.4% vs 0.7%, P = 0.02).

CONCLUSIONDespite a similar success rate of primary PCI and in-hospital outcomes in both genders, female patients with acute STEMI still have a worse prognosis during the long-term follow-up.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Sex Factors ; Treatment Outcome

BACKGROUND: Stent under-expansion and procedurally related abnormal lesion morphologies (e.g. dissection, thrombus) are associated with stent restenosis and acute, subacute and chronic thrombosis.OBJECTIVE: To explore whether larger post-procedural final minimum stent area can be acquired and more procedurally related complications can be identified in stent implantation guided by intravascular ultrasound.DESIGN, TIME AND SETTING: Retrospective analysis was performed at the Heart Center of Beijing Chaoyang Hospital, Capital Medical University between January 2004 and February 2005.PARTICIPANTS: Fifty patients with coronary artery disease with 52 lesions were enrolled in the study and underwent stenting guided by intravascular ultrasound. The patients were characterized as non-diffused lesion with vessel diameter ≥ 2.5 mm. Patients with severe left main lesion were excluded.METHODS: Qualitative and quantitative analyses were carried out in 50 patients with 52 lesions before and after stent implantation. The stent diameter and the end-point of therapy were determined by intravascular ultrasound standard.MAIN OUTCOME MEASURES: The differences of end point for stent implantation and the enlargement of lumen area gained by stent implantation were compared between cardioangiography and by intravascular ultrasound.RESULTS: The average stent diameter guided by intravascular ultrasound was larger than by cardioangiography (P=0.011); the peak balloon pressure was higher in intravascular ultrasound group than cardioangiography group (P < 0.001), and area stenosis percentage measured by quantitative coronary angiogram was smaller in intravascular ultrasound group than cardioangiography group (P=0.044). ②Cardioangiography showed success rate was 96.2% and intravascular ultrasound showed the success rate was only 37.7% after first balloon high-pressure dilation. Intravascular ultrasound subgroup analysis showed higher peak balloon pressure (P < 0.001), larger lumen diameter (P < 0.001), larger lumen area (P < 0.001), and smaller area stenosis percentage (P < 0.001). No obvious stenosis was found at the proximal and distal segments of the stent observed by cardioangiography, while atherosclerotic lesions at proximal segment were found in 39 cases (75.0%) and at distal segment were in 23 cases (44.2%) observed by intravascular ultrasound. The lumen area was larger in non-fatty plaque than in fatty plaque after stent implantation (P < 0.001). Compared with non-fatty plaque, the enlargement of vessel area was 1.30 mm2 smaller, while plaque compression was 0.48 mm2 larger. CONCLUSION: Stent implantation guided by intravascular ultrasound can acquire larger final lumen area and identify more procedurally related complications.