Post-stroke cognitive impairment (PSCI) is a common complication after stroke, which has high disability rate and mortality rate, and can affect the patient′s daily living ability and quality of life. Non-invasive brain stimulation (NIBS) has the advantages of non-invasiveness, safety, and ease of operation, and is easily accepted by patients. NIBS has a good application prospect in the treatment of PSCI, especially the representative treatment repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) such as have good clinical application effects. At present, there is no standardized treatment plan for NIBS, and there are large individual differences in therapeutic effects. This study reviewed the mechanism and clinical application of NIBS in the treatment of PSCI, and discussed the future application direction of NIBS.

OBJECTIVES: The aim of this study was to compare the anterior and posterior occlusal plane characteristics of patients with different temporomandibular joint osseous statuses. METHODS: A total of 306 patients with initial cone beam CT (CBCT) and cephalograms were included. They were divided into three groups on the basis of their temporomandibular joint osseous status: bilateral normal (BN) group, indeterminate for osteoarthrosis (I) group, and osteoarthrosis (OA) group. The anterior and posterior occlusal planes (AOP and POP) of the different groups were compared. Then, the regression equation was established after adjusting for confounding factors, and a correlation analysis between the occlusion planes and other parameters was performed. RESULTS: SNA, SNB, FMA, SN-MP, Ar-Go, and S-Go were correlated with the occlusal planes. Relative to the BN and I groups, the FH-OP of the OA group increased by 1.67° on the average, FH-POP increased by 1.42° on the average, and FH-AOP increased by 2.05° on the average. CONCLUSIONS The occlusal planes were steeper in the patients with temporomandibular osteoarthrosis than in the patients without it, and the mandible rotated downward and backward. The height of the mandibular ramus, the mandibular body length, and the posterior face height were small. In clinical practice, attention should be given to the potential risk of temporomandibular joint osteoarthrosis in such patients. In addition, SNB, FMA, SN-MP, Ar-Go, S-Go, and occlusal planes had moderate correlations.
Humans ; Dental Occlusion ; Cephalometry ; Mandible ; Temporomandibular Joint Disorders/diagnostic imaging* ; Temporomandibular Joint/diagnostic imaging* ; Osteoarthritis/diagnostic imaging* ; Mandibular Condyle

With the advances in fetal medicine, there will be more cases of congenital hypothyroidism (CH) diagnosed in the fetal period. However, there is no consensus on the management protocol. We present a successful case of conservatively managed fetal goitrous hypothyroidism due to compound heterozygous TG mutations. Goiter was observed in a fetus at 23 weeks of gestation. Because there was no evidence of transplacental passage of antithyroid antibody and drugs, iodine overload, and iodine deficiency, the fetus was highly suspected to have CH. Considering the potential risks of amniocentesis/cordocentesis, and lack of available parenteral levothyroxine in China, the fetus was closely monitored thereafter. A male neonate was delivered vaginally without complications at 39 weeks of gestation. We verified severe hypothyroidism in the infant and immediately initiated levothyroxine therapy. His growth and mental development were normal at the age of 8 month. Whole-exome sequencing showed that the neonate had two compound heterozygous mutations in the TG gene. We also performed a literature review of the prognosis of postnatal treatment of CH due to TG mutations and the result showed that postnatal treatment of CH due to TG mutations has a favorable prognosis. However, further prospective studies are warranted to verify this conclusion.

With the advances in fetal medicine, there will be more cases of congenital hypothyroidism (CH) diagnosed in the fetal period. However, there is no consensus on the management protocol. We present a successful case of conservatively managed fetal goitrous hypothyroidism due to compound heterozygous TG mutations. Goiter was observed in a fetus at 23 weeks of gestation. Because there was no evidence of transplacental passage of antithyroid antibody and drugs, iodine overload, and iodine deficiency, the fetus was highly suspected to have CH. Considering the potential risks of amniocentesis/cordocentesis, and lack of available parenteral levothyroxine in China, the fetus was closely monitored thereafter. A male neonate was delivered vaginally without complications at 39 weeks of gestation. We verified severe hypothyroidism in the infant and immediately initiated levothyroxine therapy. His growth and mental development were normal at the age of 8 month. Whole-exome sequencing showed that the neonate had two compound heterozygous mutations in the TG gene. We also performed a literature review of the prognosis of postnatal treatment of CH due to TG mutations and the result showed that postnatal treatment of CH due to TG mutations has a favorable prognosis. However, further prospective studies are warranted to verify this conclusion.

Postoperative hydrocephalus is one of the most common complications in resection of lateral ventricle trigone tumor, which can seriously affect the prognoses of patients. Possible influencing factors include tumor resection degrees, postoperative meningitis, intraoperative intraventricular hemorrhage, and cerebrospinal fluid drainage tube placement, but the specific mechanism is still unclear. In this paper, the influencing factors and possible mechanisms of hydrocephalus after lateral ventricle trigone tumor are reviewed as follows.

Objective To explore the value of prenatal ultrasound in diagnosis of omphalocele-exstrophy-imperforate anusspinal defects (OEIS) in first trimester.Methods Prenatal ultrasonic characteristics of 10 fetuses with OEIS complex in first trimester were retrospectively analyzed and compared with autopsy results.Results Cystic bulging in the lower anterior abdominal wall was observed in all 10 fetuses.Spinal scoliosis dysplasia was found in 10 fetuses,with myelomeningocele in 3 fetuses.No normal bladder was visualized in 8 fetuses.Thickened nuchal translucency was noticed in 5 fetuses,among which neck lymphatic hydrocele was found in 1 fetus.The bilateral clubbed feet and left lower mutilation was observed in 1 fetus,respectively.All 10 OEIS complex fetuses were found accompanied with short umbilical cord,while single umbilical artery and umbilical cord cyst were found in 4 and 1 fetus,respectively.Autopsy showed abdominal wall defects with exstrophy in 10 fetuses.However,no complete cystic bulging was found.Besides,autopsy also showed pubic symphysis separation and bladder exstrophy in 10 fetuses without obvious genitalia nor anus.Conclusion Cystic bulging in the lower anterior abdominal wall is the most common prenatal ultrasonic characteristic of OEIS complex in first trimester.

Objective To investigate the value of clinical follow-up in prenatal diagnosis of isolated double aortic arch (DAA) . Methods The clinical follow-up materials were retrospectively reviewed in 17 fetuses . Of all the isolated DAA fetuses ,the accuracy rate of prenatal diagnosis was confirmed by CT ,MRI , autopsy or echocardiography ,and pregnant outcomes were summarized . Results A total of 17 fetuses had a sonographic diagnosis of isolated DAA in our centers at a mean gestational age of 23 -32(27 ± 3) weeks , with mother mean age 19 -44 (28 ± 6) years old . One case of DAA type-A was misdiagnosed ,15 cases were delivered with 2 cases occurred respiratory distress or mild dysphagia ,who received surgical treatment , and 13 cases clinical findings were unremarkable at the fellow-up of 24 months ,the silent-rate of clinical symptoms was 86％ . Termination of pregnancy happened in 2 cases ,with 1 (6％ ) had additional ventricular septal defects ,another ( 6％ ) had additional anomalies of congenital high airway obstruction syndrome . In 17 cases of fetuses with isolated DAA ,there were 15 ( 88％ ) cases with dominant right-sided arch ,1 case (6％ ) with dominant left arch ,and 1 case (6％ ) with equal arches in size .Karyotyping prenatal testing was offered to 15 parents with normal results . Conclusions Prenatal ultrasound can accurately diagnose isolated DAA by multiple sections scan ,expanding diagnostic ideas by combination with other medical imaging data to prevent apparent life-threatening event ,or to guide for ex-utero intrapartum treatment . Isolated DAA clinical follow-up results in good outcome .

Objective: To establish a triple-color pseudovirion-based neutralization assay (PBNA) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of HPV 9-valent vaccine. Methods: HPV pseudovirus (PsVs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid N31-MCHREEY, green fluorescent N31-EGFP or blue fluorescent N31-mTagBFP were generated. The concentration of HPV PsVs and the infection titers of HPV PsVs were detected by double-antibody sandwich ELISA and TCID₅₀, respectively. The single- and triple color HPV 16/33/45 PsVs were used to detect the neutralization titers of mice sera immunized with HPV 9-valent vaccine and confirmed the accuracy and specificity of the triple-color PBNAs. Then, the single- and triple color HPV 6/11/18/31/33/45/52/58 PsVs were employed to detect the neutralization titers of cynomolgus macaques sera immunized with HPV 9-valent vaccine and determined whether the triple-color PBNAs could be applied to evaluate the immunogenicity of the sera generated by the immunization of HPV9-valent vaccine. Results: The concentration of HPV16 PsVs encapsulating green, red or blue fluorescent plasmid was 5.0 to 6.0 μg/ml and HPV6/11/18/31/33/45/52/59 triple-color HPV PsVs was about 1.0 to 3.0 μg/ml. 9 types HPV PsVs containing EGFP, Mcherry or mTagBFP reporter plasmid were obtained and the concentration can meet the need of neutralization detection. 9 types single-color fluorescent HPV PsVs had similar infectivity against 293FT cells with the infection titer values between 1×10⁴ and 1×10⁵. The results of PBNAs showed that there was no significant difference in the anti-HPV neutralization titers of mice sera induced by HPV 9-valent vaccine between single-color and triple-color HPV16/33/45 PsVs (P>0.05). Similarly, there was also no significant difference in the anti-HPV neutralization titers of cynomolgus macaques sera induced by HPV 9-valent vaccine between single-color and triple-color HPV6/11/18/31/33/45/52/58 PsVs (P>0.05). Conclusion We successfully established the triple-color PBNAs and verified the accuracy and specificity of triple-color PBNAs consistent with single-color PBNAs. The triple-color PBNAs can be applied to evaluate the immunogenicity of HPV 9-valent vaccine's immune serum.

Background: Oral cancer is a common type of head and neck cancers. Knowing its epidemiologic characteristics is crucial to preventing, diagnosing, and treating this cancer. This study aimed to explore the epidemiologic characteris?tics of oral cancer in South China. Methods: We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat?sen University Cancer Center between 1960 and 2013. We compared the age of onset, sex ratio, pathologic type, and primary tumor location among three subcultural areas (Guangfu, Hakka, and Chaoshan) and between an economically developed region and a less?developed one in Guangdong. Results: Overall, oral cancer had a male?to?female ratio of approximately 2:1, and this ratio decreased over time. Oral cancer occurred mostly in patients of 45–64 years old (54.5%), and the percentage of older patients gradually increased over time. The most common tumor location was the tongue. Squamous cell carcinoma was the predomi?nant pathologic type. The percentage of blood type O in oral cancer patients was lower than that in the healthy pop?ulation. The male?to?female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas, whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan. The male?to?female ratio was lower and the age of disease onset was higher in the economically developed region than in the less?developed region. Conclusion: The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

OBJECTIVEThe aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens.

METHODSLung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens.

RESULTSAmong the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance.

CONCLUSIONSThe standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion.

Adenocarcinoma ; drug therapy ; enzymology ; genetics ; pathology ; Alkaline Phosphatase ; genetics ; metabolism ; Gene Fusion ; Genes, erbB-1 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Protein Kinase Inhibitors ; therapeutic use ; Proteomics ; Pyrazoles ; therapeutic use ; Pyridines ; therapeutic use ; Sensitivity and Specificity