Suboptimal treatment of laryngeal squamous cell carcinoma (LSCC) provides poor survival rate. The poor bioavailability, resistance to cetuximab (Cet), and the instability of small interfering RNA (siRNA) limit their efficacy in LSCC therapy. The present study has been aimed to develop a Cet and focal adhesion kinase (FAK) siRNA (siFAK) co-delivery nanosystem. Zeolitic imidazolate framework-8 (ZIF-8), with its large specific surface area and pH-responsive properties, is an ideal delivery carrier allowing controlled drug release in the acidic tumor microenvironment. Therefore, Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane (TCM) after the electrostatic adsorption of siFAK. Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, X-ray diffraction, and particle size analyses were deployed to characterize Cet/siFAK@ZIF-8@TCM. TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake, cytotoxicity, in vivo biocompatibility, biodistribution, biosafety, pH responsiveness, and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM. After ZIF-8@TCM were loaded with Cet and siFAK, alterations in their physical and crystal structures, particle size, and zeta potential were observed. Meanwhile, the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8. The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation, effectively decreasing the messenger RNA (mRNA) and protein expression levels of FAK in LSCC cells. The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pH-responsiveness and tumor-targeting capabilities, thereby exerting anti-LSCC effects. Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene, in turn maximizing their anti-LSCC effect while ensuring biosafety.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a neonate with Au-Kline syndrome (AKS). METHODS: Clinical data and result of genetic testing of a neonate with AKS who was admitted to the Affiliated Provincial Children's Hospital of Anhui Medical University in January 2021 were retrospectively analyzed. Relevant literature was searched from the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed databases using key words "Au Kline syndrome", "Au-Kline syndrome", "HNRNPK" and "AKS". The research period was set as from January 1, 2000 to December 31, 2020. RESULTS: The male newborn has manifested feeding difficulties, hypotonia, absence of the upper jaw to the uvula and facial dysmorphism. Trio-whole exome sequencing revealed that he has harbored a frameshift c.478dupA (p.Ile160AsnfsTer7) variant of the HNRNPK gene, which was varified by Sanger sequencing to have a de novo origin. The variant has not been included in the databases. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). Literature retrieval has identified 14 children with AKS and de novo mutations of the HNRNPK gene. Their clinical manifestations have included growth and motor retardation, various degree of mental retardation, facial dysmorphism and a high frequency of congenital heart malformations. CONCLUSION The AKS in this child may be attributed to the c478dupA frameshifting variant of the HNRNPK gene. Diagnosis of AKS should be suspected for children with mental retardation and multiple congenital malformation syndromes including Kabuki syndrome.
Humans ; Male ; Abnormalities, Multiple/genetics* ; Genetic Testing ; Heterogeneous-Nuclear Ribonucleoprotein K/genetics* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Infant, Newborn

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca 2+ /P 5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

Objective To investigate the clinical effect of mifepristone and misoprostol combined with hysteroscopic resection of endometrial uterine incision cesarean scar pregnancy.Methods A retrospective study was conducted to analyze 135 cases of scar pregnancy of endogenous lower uterine cesarean section from January 2015 to October 2017.According to the treatment methods,they were divided into group A (mifepristone and misoprostol combined with hysteroscopy),group B (methotrexate combined with hysteroscopy),group C (Uterine artery embolization + curettage).Each group had 45 cases,and the therapeutic effects of the three methods were compared.Results There was no significant difference in gestational sac size and serum human chorionic gonadotropin [beta-human chorionic gonadotropin (HCG)] levels among the three groups before operation (P ＞ 0.05).After operation,the operation time,intraoperative bleeding volume,serum beta-HCG dropping to normal time,vaginal bleeding time and hospitalization time in A and C group were significantly lower than that in B group (P ＞ 0.05).There was no significant difference between group A and group C in operation time,serum beta-HCG to normal time,vaginal bleeding time and hospitalization time.(P ＞ 0.05).The menstruation time of group A was significantly shorter than that of group B and group C (P ＜0.05).The effective rates of group A,B and C were 100.00％,97.78％ and 100.00％ respectively,with no significant difference in the three groups (P ＞ 0.05);The complication rates of A,B and C groups were 2.22％,13.33％ and 4.44％ respectively,with no significant difference in the three groups (P ＞ 0.05).Conclusions The three methods are effective in the treatment of cesarean scar pregnancy.The mifepristone and misoprostol combined with hysteroscopy have the advantages of less operative trauma and faster postoperative recovery.

Objective To explore the curative effect and nursing of enhanced external counterpulsation (EECP) on patients with ischemic cerebral apoplexy. Methods In September 2013 to March 2013 in Shenzhen Futian District People′s Hospital neurology hospital, toally 286 patients with ischemic cerebral apoplexy were randomly divided into two groups, control group and treatment group with 143 cases in each group. The control group used conventional treatment and the treatment group used EECP. The score of clinical nerve function and defect improved Barthel index were compared. Result The score of clinical nerve function defect and improved Barthel index of the treatment group before the treatment were without difference (all P>0.05). The score of clinical nerve function defect and improved Barthel index of the treatment group were less than those of control group after the treatment (all P < 0.05). Conclusion Ischemic stroke patients with positive EECP can significantly increase clinical neural function and life ability , improve patient′s quality of life.

Objective To investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-dC) alone or combined with trichostatin A(TSA) on cell proliferation, promoter methylation and mRNA expression level of PDX-1 gene in pancreatic β cells induced by high glucose toxicity. Method NIT-1 cells were treated in vitro by high glucose (33.3 mmol/L), then divided into five groups, control group, HG grpup, 5-Aza-dC treatment group, TSA interfere group and 5-Aza-dC + TSA group. Proliferation of NIT-1 cells, insulin secretion, promoter methylation and mRNA expression of PDX-1 gene were detected respectively. Results 5-Aza-dC and TSA alone or in combination could promote cell proliferation and recover insulin secretion in NIT-1 cells , could also reduce PDX-1 gene methylation and enhance expression of PDX-1 mRNA. Compared with single-treatment group , combined group was significantly different (all P < 0.05). Conclusion 5-Aza-dC and TSA could activate the expression of PDX-1 and, then recover insulin secretion in NIT-1 cells induced by high glucose. Combination of them had synergistic effect.

Objective To study the granulocyte colony stimulating factor ( G-CSF ) and granulocyte macro-phage colony stimulating factor ( GM-CSF) in complete remission of acute myeloid leukemia ( AML) patients with den-dritic cells(DC)changes in the function and its subsets .Methods 36 cases of complete remission according to AML patients were randomly divided into 3 groups,G group was given G-CSF 200g/d,subcutaneous injection ,GM group were given GM-CSF 200g/d,subcutaneous injection ,the control group were injected with normal saline .The curative effects were compared.Results The expression of G in group DC,CD83 and CD86 on surface of CD80 were lower than that in GM group and C group (t=4.34,5.43,4.54,4.54,5.25,3.54,all P<0.05),GM group,DC expression of CD11c was higher than that of G group and C group (t=4.54,4.27,all P<0.05).G group and GM group DC in promoting lymphocyte proliferation were higher than those in C group (t=4.54,5.64,all P<0.05);group GM DC to promote the ability of CD4 +T lymphocyte proliferation was higher than that of G group (t=3.54,P<0.05).ELISA assay,GM group DC secretion of IL-12 than that of group G and C group;group G DC secretion of IL-10 was higher than that of GM group and C group (t=3.54.4.23,4.32,3.87,all P<0.05).Conclusion G-CSF and GM-CSF can make the complete remission in patients with AML subgroup DC shift ,the bias of G-CSF DC2 and certain immuno-suppressive effect ,while GM-CSF DC subsets of DC 1 and promotes cell immune deviation .

Objective To explore the relationship between HBV-DNA load and the offspring vertical transmission of HBV.Methods 138 families who had taken the examination between August 2009 and November 2011 but the HBsAg of the housewife was negative,were chosen as research objects.Blood from the couples and sperms from the husbands during pregnancy were followed and collected for detection on related indicators.Cord blood was sampled after delivery for HBVM and HBV-DNA quantification.Those with HBV-DNA load ≥5 × 102 copies/ml were chosen as cases while those ＜5 × 102 copies/ml were formed as controls,respectively.Results 1) The positive rates of HBV-DNA was 34.8％ (48/138) in the neonatal cord blood while the positive rates of cord blood HBsAg and HBeAg were 28.3％ (39/138) and 15.2％ (21/138) respectively.2) The positive rate of semen HBV-DNA was 21.0％ (29/138) while the positive rates of paternal serum HBV-DNA and HBeAg were 76.8％ (106/138)and 42.8％ (59/138).3)Among the positive ones on paternal serum HBV-DNA,paternal serum HBeAg,semen HBV-DNA,items as measures taken for HBV vertical transmission and prevention on the fathers and the first class family histories on HBV appeared to be the risk factors for HBV paternal transmission (P＜0.05).4)Data from Multivariate analysis showed that positivities on patemal serum HBV-DNA,paternal serum HBeAg and semen HBV-DNA were risk factors for HBV paternal transmission (OR=5.7,95％CI:1.1-29.1 ; OR=4.2,95％CI:1.7-10.0; OR=6.7,95％ CI:2.4-18.9).5)Dose-response relationships were seen between levels of paternal serum HBV-DNA load and cord blood HBV-DNA load,between levels of paternal serum HBV-DNA load and semen HBV-DNA load,between levels of semen HBV-DNA load and cord blood HBV-DNA load.6)Results from the analysis on ROC curve showed that paternal serum HBV-DNA load level (105 copies/ml) and semen HBV-DNA load level (103 copies/ml)were better demarcation points to forecast the occurrence of paternal transmission of HBV,because of the better sensitivity and specificity they had.Conclusion Items as positives on paternal serum HBV-DNA,paternal serum HBeAg and semen HBV-DNA were risk factors for HBV paternal transmission.When paternal serum HBV-DNA load ＞ 105 copies/ml and semen HBV-DNA load ＞ 103 copies/ml appeared,the positive rate of HBV paternal transmission would increase.

OBJECTIVE: To evaluate the relationship between human papilloma virus (HPV) infection and the occurrence, recurrence and malignant transformation of nasal inverted papilloma (NIP). METHOD: With comprehensive retrieval of related literature that had been published in databases included Pubmed (1990--2011), Cochrane Library, CNKI (1979-2011), VIP (1989-2011), CBM (1990-2011) and WANFANG Meta-analysis software Rev-Man 5.0 was used to analyze the raw data and to calculate the value of combined odd ratio (OR) and 95% confidence interval (CI). RESULT: According to Meta-analysis, the occurrence group between HPV and NIP, the OR was 34.44 and 95% CI was 12.96-91.56; the recurrence group, the OR was 3.66 and 95% CI was 1.77-7.56, to the high-risk HPV, the OR was 1.94 and 95% CI was 0.30-12.58; the malignant transformation group, the OR was 1.79 and 95% CI was 0.94-3.40 to the high-risk HPV, the OR was 49.35 and 95% (CI was 0.45-11.23. CONCLUSION HPV may play an important role in the occurrence and recurrence of NIP and high-risk HPV was closely related to the progress of NIP.
DNA, Viral ; Humans ; Nose Neoplasms ; virology ; Papilloma, Inverted ; virology ; Papillomaviridae ; Papillomavirus Infections ; pathology

Objective To explore whether the stimulation effect of high phosphate on hyperplasia of human parathyroid cells and hyperparathyroidism through local cyclooxygenase 2 (COX2) up-regulation pathway. Methods Parathyroid glands were collected from 19 uremic patients undergoing parathyroidectomy.Expressions of COX1,COX2 and proliferative cell nuclear antigen (PCNA) of the glands were detected by immunohistochemistry.Primary parathyroid cells were cultured and treated with high or normal phosphate for 48 hours.Then expressions of COX2 and PCNA were detected by Western blotting and real-time PCR. Results Among 62 glands from above 19 patients,43 glands were nodular hyperplasia and 19 diffuse hyperplasia.Both high expressions of COX2 and PCNA were found in these blands.Expression of COX2 was found in both oxyphil and chief cells and was more in the diffuse hyperplasia glands than that in the nodular hyperplasia (P＜0.05).80.60％ and 85.20％ of COX2 positive cells in diffuse hyperplasia glands and nodular hyperplasia also expressed PCNA. High phosphate could stimulate iPTH secretion in vitro (P＜0.05).Expressions of COX2 and PCNA were higher in high phosphate group.(P＜0.05). Conclusion High phosphate may stimulate the hyperplasia of parathyroid cells by up-regulating the local COX2 expression.