Relationship between the CT features of colorectal cancer metastases calcification and tumor response to chemotherapy / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between CT features of metastatic calcification and the response to chemotherapy in colorectal cancer metastases.@*METHODS@#A total of 27 patients with 30 sites of calcified metastases who underwent chemotherapy combined with targeted therapy (cetuximab) between January 2011 and December 2016 comprised this retrospective study population. Two radiologists independently evaluated the occurrence of tumor calcification before and after treatment, and evaluated the tumor response after therapy. According to the response evaluation criteria in solid tumors (version 1.1), the best curative effect evaluation of the patients was recorded. The patients were divided into groups as below: (1) Patients who showed complete response (CR) and partial response (PR) were assigned to the response group, and the stable disease (SD) and progressive disease (PD) were assigned to the non-response group. (2) Patients showed CR or PR, or patients showed SD with longer progress free survival (PFS) were assigned to the benefit group, and the remaining patients were assigned to the no benefit group. The difference of different imaging calcification features (morphology, maximum density, and density-time slope) were analyzed.@*RESULTS@#The most common site of metastases calcification was liver (63.3%), followed by lymph nodes (26.7%). There were 12 cases in the response group, 15 cases in the non-response group; and 13 cases in the benefit group, 14 cases in the no benefit group. The density time growth slope was higher in the response group when compared with the non-response group (P=0.025). The proportion of thhe patients with increased number of calcified foci in the benefit group (61.5%) was higher than that in the no benefit group (14.3%), P=0.018. There was no significant difference in the maximum density between the groups. The calcification of liver metastases were all amorphous calcification, with central calcification (36.8%), eccentric calcification (36.8%), garland calcification (15.8%) and diffuse calcification (10.6%). The lymph node metastases could be diffuse (75.0%), and curve or eggshell calcification (25.0%). There was no statistical difference between the groups.@*CONCLUSION@#In patients with advanced colorectal cancer metastases treated with cetuximab combined chemotherapy, rapid growth of calcification density and increased calcification number may be valuable imaging features of therapeutic efficacy. The maximal calcification density and morphology of calcification are not related to the therapeutic efficacy.

A case report and analysis of hypertrophic obstructive cardiomyopathy causing an illusion of aortic stenosis.

RATIONALE: This study aimed to report a case of hypertrophic obstructive cardiomyopathy causing an illusion of aortic stenosis on imaging. PATIENT CONCERNS: A 71-year-old woman presented with chest tightness after activity for 1 year and coughing for 2 months. A systolic 3/6 grade murmur was found in the third intercostals of the left border of sternum. Transthoracic echocardiography, transesophageal echocardiography, and magnetic resonance imaging (MRI) were all suggestive of aortic stenosis and left ventricular outflow tract stenosis. DIAGNOSIS: The patient was diagnosed with "severe aortic stenosis (bicuspid deformity), left ventricular outflow tract stenosis (moderate), and grade II cardiac function." She was advised aortic valve replacement and left ventricular outflow tract dredging. However, no aortic valve lesion was found during the operation, and the diagnosis was changed to "hypertrophic obstructive cardiomyopathy." INTERVENTIONS AND OUTCOMES: The morrow procedure was performed, and the patient recovered well after the operation. Hypertrophic obstructive cardiomyopathy was found to cause an illusion of aortic stenosis on imaging. LESSONS: Special attention and rational treatment should be paid to such patients. In addition, further studies are needed to distinguish between the two diseases to reduce misdiagnosis.

Implementing the communication for development strategy to improve knowledge and coverage of measles vaccination in western Chinese immunization programs: a before-and-after evaluation.

BACKGROUND: Communication for Development (C4D) is a strategy promoted by the United Nations Children's Fund to foster positive and measurable changes at the individual, family, community, social, and policy levels of society. In western China, C4D activities have previously been conducted as part of province-level immunization programs. In this study, we evaluated the association of C4D with changes in parental knowledge of immunization services, measles disease, and measles vaccine, and changes in their children's measles vaccine coverage. METHODS: From April 2013 to April 2014, C4D activities were implemented as part of provincial immunization programs in the Inner Mongolia, Guangxi, Chongqing, Guizhou, Tibet, Shaanxi, Gansu, Ningxia, and Qinghai provinces. We used a before-and-after study design and employed face-to-face interviews to assess changes in parental knowledge and vaccination coverage. RESULTS: We surveyed 2 107 households at baseline and 2 070 households after 1 year of C4D activities. Following C4D, 95% of caregivers were aware of the vaccination record check requirement for entry into kindergarten and primary school; 80% of caregivers were aware that migrant children were eligible for free vaccination; more than 70% of caregivers knew that measles is a respiratory infectious disease; and 90% of caregivers knew the symptoms of measles. Caregivers' willingness to take their children to the clinic for vaccination increased from 51.3% at baseline to 67.4% in the post-C4D survey. Coverage of one-dose measles-containing vaccine (MCV) increased from 83.8% at baseline to 90.1% after C4D. One-dose MCV coverage was greater than 95% in the Guangxi, Shaanxi, and Gansu provinces. Two-dose MCV coverage increased from 68.5 to 77.6%. House-to-house communication was the most popular C4D activity among caregivers (91.6% favoring), followed by posters and educational talks (64.8 and 49.9% favoring). CONCLUSIONS: C4D is associated with increased caregiver knowledge about measles, increased willingness to seek immunization services for their children, and increased measles vaccination coverage. Tailored communication strategies based on insights gained from these analyses may be able to increase vaccination coverage in hard-to-reach areas. C4D should be considered for larger scale implementation in China.

Immunogenicity of Two Different Sequential Schedules of Inactivated Polio Vaccine Followed by Oral Polio Vaccine Versus Oral Polio Vaccine Alone in Healthy Infants in China.

BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule. METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored. RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar. CONCLUSIONS: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011.

BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.

Cross-border collaboration between China and Myanmar for emergency response to imported vaccine derived poliovirus case.

BACKGROUND: This report describes emergency response following an imported vaccine derived poliovirus (VDPV) case from Myanmar to Yunnan Province, China and the cross-border collaboration between China and Myanmar. Immediately after confirmation of the VDPV case, China disseminated related information to Myanmar with the assistance of the World Health Organization. METHODS: A series of epidemiological investigations were conducted, both in China and Myanmar, including retrospective searches of acute flaccid paralysis (AFP) cases, oral poliovirus vaccine (OPV) coverage assessment, and investigation of contacts and healthy children. RESULTS: All children <2 years of age had not been vaccinated in the village where the VDPV case had lived in the past 2 years. Moreover, most areas were not covered for routine immunization in this township due to vaccine shortages and lack of operational funds for the past 2 years. CONCLUSIONS: Cross-border collaboration may have prevented a potential outbreak of VDPV in Myanmar. It is necessary to reinforce cross-border collaboration with neighboring countries in order to maximize the leverage of limited resources.

Congenital heart surgery in patients with ventricular noncompaction.

BACKGROUND: Noncompaction of the ventricular myocardium (NVM) is exceedingly rare and associated with a high morbidity and mortality. This pathology has been associated with other congenital heart diseases (CHDs). The efficacy of surgical treatment of patients with NVM and other CHDs is largely unknown. The aim of the present study was to describe surgical outcomes of 16 patients. METHODS AND RESULTS: Between April 2009 and October 2011, 16 patients with NVM and CHD were admitted to our hospital. Through a clinical chart review, we analyzed results of surgical treatment of NVM with other CHDs retrospectively. The median age was 3.9 years (range 2 m-11 y). The follow-up time was 23.93 months (range 3 m-36 m). Two patients (12.5%) died after the surgery, the remaining patients (87.5%) had an uneventful postoperative course. An additional patient died due to sudden death three months after surgery. Two patients developed recurrent heart failure after surgery. Congestive heart failure, severe arrhythmias, and the range of NVM may be risk factors for death. At 6 months after the operation, the NYHA functional class was significantly improved (2.38 ± 0.89 vs. 1.62 ± 0.65, p = 0.009). The cardiothoracic ratio was significantly reduced when compared to before the operation (p < 0.001). CONCLUSIONS: Surgery in patients with NVM and other CHDs can be effective in relieving heart failure, improving heart function, and decreasing heart size.

An outbreak of type π vaccine-derived poliovirus in Sichuan province, China: emergence and circulation in an under-immunized population.

BACKGROUND: During August 2011-February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. METHODS: A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. RESULTS: One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8-1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5-12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February-May, 2012, and the strain has not been isolated since. CONCLUSION: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.

Poliomyelitis eradication in China: 1953-2012.

BACKGROUND: Poliomyelitis has historically been endemic in China and has been considered an important cause of disability and death. METHODS: We reviewed strategies and measures of poliomyelitis control and eradication from 1953 to 2012. Data from notifiable disease and routine immunization reporting systems and acute flaccid paralysis (AFP) surveillance were analyzed. RESULTS: About 20 000 poliomyelitis cases were reported annually in the prevaccine era. During 1965-1977, live, attenuated oral poliomyelitis vaccine (OPV) was administered to children through annual mass campaigns in the winter, and the number of poliomyelitis cases started to decline. A cold chain system was established during 1982, and OPV coverage increased during the early stage of the Expanded Programme on Immunization, from 1978 to 1988. Between 1989 and 1999, routine immunization was strengthened, supplementary immunization activities (SIAs) were conducted, and the AFP surveillance system was established. China reported a last indigenous poliomyelitis case in 1994 and was certified as free of polio in 2000. To maintain its polio-free status, China kept >90% coverage of 3 doses of OPV, conducted SIAs in high-risk areas, and maintained high-quality of AFP surveillance. China succeeded in stopping the outbreak in Xinjiang in 2011. CONCLUSIONS: China's polio-free status was achieved and maintained through strengthening routine immunization and implementing SIAs and AFP surveillance.

Enhanced surveillance of acute flaccid paralysis following importation of wild poliovirus in Xinjiang Uygur Autonomous Region, China.

BACKGROUND: After being polio free for more than 10 years, an outbreak occurred in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the importation of wild poliovirus (WPV) originating from neighboring Pakistan. METHODS: To strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang, "zero case daily reporting" and retrospective searching of AFP cases were initiated after the confirmation of the WPV outbreak. To pinpoint all the polio cases in time, AFP surveillance system was expanded to include persons of all ages in the entire population in Xinjiang. RESULTS: Totally, 578 AFP cases were reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases were reported among adults aged 15-53 years. Strengthening AFP surveillance resulted in an increase in the number of non-polio AFP cases in 2011 (148 children < 15 years) compared with 76 cases < 15 years in 2010. The AFP surveillance system in Xinjiang was sensitive enough to detect polio cases, with the AFP incidence of 3.28/100,000 among children < 15 years of age. CONCLUSIONS: Incorporating adult cases into the AFP surveillance system is of potential value to understand the overall characteristics of the epidemic and to guide emergency responses, especially in countries facing WPV outbreak following long-term polio free status. The AFP surveillance system in Xinjiang was satisfactory despite limitations in biological sample collection.

Identification and control of a poliomyelitis outbreak in Xinjiang, China.

BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels / 华中科技大学学报（医学）（英德文版）

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.

Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels / 华中科技大学学报（医学）（英德文版）

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.