Objective To report the clinical manifestation and gene mutation of congenital insensitivity to pain with anhidrosis (CIPA) in two patients from one family. Methods The data of clinical manifestation, laboratory examination, and family history of two patients were collected. The peripheral blood of patients and their parents were collected. Neurotrophic tyrosine kinase receptor type 1 (NTRK 1 ) gene was detected directly by Sanger method, the pathogenicity of the mutation in the gene was analyzed by bioinformatics. Results Both of patients were female and mainly suffered with reduplicated non-infectious fever, anhidrosis, insensitive to pain, and mental retardation. The proband had fracture many times after minor injury. The ninth exon of NTRK 1 genes in the proband and her younger sister were found to have heterozygous mutations, c. 851-33 T>A, as previously reported. Meanwhile, there was also found a new mutation, c. 1711 G>A (p.G 571 S), in thirteenth exon of NTRK 1 genes in these two patients. It was predicted to be a harmful mutation by bioinformatics and the mutation site is conservative. Their father and mother were found carrying the c. 851-33 T>A and c. 1711 G>A mutations respectively. Conclusion Both patients had typical clinical manifestations. And the newly discovered p.G 571 S mutation expands the mutation spectrum of NTRK 1 gene.

Objective To discuss microsurgical experience for transsuboccipital retrosigmoid sinus approach of large acoustic neuronomas,and improve the rate of tumor removing,and facial nerve and auditory nerve preserving Methods A retrospective analysis of 39 patients with acoustic neuronomas which were more than 4 cm in diameter were treated by microsurgery between January 1994 and December 2000 Tumor's excision was performed by transsuboccipital retrosigmoid sinus approach The surgical main points of transsuboccipital retrosigmoid sinus approach,and their experience of total removal,and rate of facial nerve and auditory nerve preservation were described Results The tumors were totally removed microsurgically in 34 patients,the total removal rate was 87 2%,and subtotal removal in 5 patients Facial nerve was anatomically preserved in 31 cases,the rate of facial nerve preservation was 79 5%,but the function of facial nerve was recovered in 22 cases (56 4%) The auditory nerve was preserved anatomically in 15 cases (38 5%) and functionally in 7 cases (17 95%) Conclusions An minimally invasive microsurgical treatment are crucial for increasing a satisfactory living quality of the patients It is considered that the total removal rate of tumor,the preservative rate of facial nerve and auditory depend upon microsurgical technique and intraoperative facial nerve monitoring in acoustic neuromas surgery

Objective To screen the potential biomarkers in plasma of rats with acute paraquat (PQ) poisoning using gas chromatography-mass spectrometry (GC-MS) based metabonomics technology,and to provide concrete evidence for early diagnosis.Methods Eight Sprague-Dawley (SD) rats were randomly divided into PQ poisoning group (intragastricly administrated with PQ solution 100 mg/kg) and control group (intragastricly administrated with the same volume of normal saline) according to the random number table,with 4 rats in each group.The general situation of rats was observed at 2,24 and 48 hours after administration.The blood of eye sockets was collected,the endogenous small molecule metabolites in plasma were determined with GC-MS method,and metabolic profile analysis and random forest analysis were performed to filter the potential biomarkers.Results ① The rats in PQ poisoning group gradually appeared lack movement,tachypnea,abdominal seizure and other symptoms of poisoning.In control group,the vital signs were stable.② The metabolites in plasma of rat were analyzed with GC-MS analysis,and the diagrammatic figure was plot as combined with principal component analysis (PCA) and partial least squares-discriminated analysis (PLS-DA) model,which showed that the distribution of plasma metabolism in PQ poisoning group was more diffuse but in the control group was more intensive,indicating that the metabolic patterns in two groups were different.From 2 hours after PQ administration,the metabolic trajectory in PQ poisoning group was significantly deflected compared with that of the control group,which was similar to control group until 48 hours,indicating that the metabolites in plasma of rat showed obvious difference in the early period.Five kinds of potential biomarkers with large weights were selected by random forest method which were serine,L-asparagine,hexadecanoic acid,octadecanoic acid,and arachidonic acid,the retention time was 15.259,24.345,33.334,37.695,and 40.254 minutes,respectively.The levels of serine,L-asparagine,arachidonic acid in PQ poisoning group were significantly higher than those of the control group,peaked at 48,48 and 24 hours,respectively (40.884-5.38 vs.28.85±2.32,6.61±1.31 vs.0.76±0.65,14.21±4.28 vs.4.42±1.19,all P ＜ 0.01),and the levels of hexadecanoic acid and octadecanoic acid were significantly lowered,reached tough at 48 hours (39.09 ± 10.23 vs.83.99 ± 20.49,44.03 ± 3.60 vs.140.76 ± 73.91,P ＜ 0.05 and P ＜ 0.01).The changes in these biomarkers were related to the toxicity of PQ,indicating that PQ could interfere the energy and lipid metabolism in rats.Conclusion Combine with the metabonomics analysis,screened plasma serine,L-asparagine,arachidonic acid content in PQ poisoning rats increased significantly,and hexadecanoic acid and octadecanoic acid content decreased significantly,which can preliminary diagnose acute PQ poisoning with animal general performance.

Objective To explore the role and mechanism of microRNA-15b in the regulation of epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods PCR assay was used to determine the expression of microRNA-15b in the HMrSV5 induced by 138mmol/L high glucose for 24 h.MicmRNA-15b mimic or inhibitor was transfected into human peritoneal mesothelial cells (HMrSV5) to over-express or down-regulate microRNA-15b.The cells were then incubated with 138 mmol/L high glucose for 24 h,and the expressions of E-cadherin(E-Cad),Vimentin (VIM),Fibronectin(FN) and Smad7 were detected by real-time PCR and Western blotting respectively.Results microRNA-15b in the HMrSV5 ceils was over-expressed and down-regulated.Increased level of microRNA-15b was obtained in HMrSV5 cells treated with high glucose.In vitro,high glucose led to the up-regulation of vimentin as well as fibronectin and the down-regulation of E-cadherin in HMrSV5 cells (all P ＜ 0.05),which indicated EMT and fibrosis.Suppression of microRNA-15b by transfection with microRNA-15b inhibitor partially reversed the EMT and fibrosis changes (P ＜ 0.05),while over-expression of microRNA-15b by transfection with microRNA-15b mimic obviously enhanced the EMT and fibrosis changes (P ＜ 0.05).Conclusions MicroRNA-15b mediates high glucose induced EMT in human peritoneal mesothelial cells by the inhibition of Smad7 possibly.MicroRNA-15b maybe a new target for the prevention and treatment of peritoneal fibrosis during peritoneal dialysis (PD).

ObjectiveTo investigate the relationship between tumor-infiltrating mast cell (TIM) and the clinicopathological and prognostic factors of patients with colorectal cancer.MethodsA total of 282 cases of paraffin-embedded colorectal cancer specimens were obtained from the First Affiliated Hospital of Sun Yat-sen University from January 2002 to December 2005.The density of TIM was determined by immunohistochemical staining.According to the mean TIM density detected [ ( 8.4 + 6.5 )/HPF ],all the patients were divided into low-TIM density group (mean TIM density ＜8.4/HPF) and high-TIM density group (mean TIM density ＞8.4/HPF).The clinicopathological factors and the prognosis of patients between high-TIM density group and low-TIM density group were compared.All data were analyzed using the t test or chi-square test.The survival curve was drawn using the Kaplan-Meier method,and the survival of the patients was analyzed by the Log-rank test.The clinicopathological factors were analyzed retrospectively with the univariate and multivariate COX regression model.ResultsTIM was detected in all the patients with colorectal cancer.Significant differences were observed in the number of patients in N stage and TNM stage between patients in the high-TIM density group and those in the lowTIM density group (x2 =6.025,7.410,P ＜ 0.05 ).All patients were followed up till September 2010,the 5-year overall and tumor-free survival rates of patients were 82.9％ and 63.1％ in the low-TIM density group,79.0％ and 59.3％ in the high-TIM density group,with significant difference between the 2 groups (P ＜ 0.05 ).COX proportional hazard regression model revealed that high density of TIM was associated with short overall survival time and tumor-free survival time of colorectal cancer patients ( RR =2.119,95 ％ CI 1.326- 3.386; RR =2.084,95 ％ CI 1.357-3.199,P ＜0.05).The resuhs of multivariate analysis showed that high density of TIM was the independent factor influencing the overall survival time and tumor-free survival time (RR =1.651,95％ CI 1.009-2.702; RR =1.680,95％ CI 1.074-2.629,P ＜ 0.05 ).ConclusionHigh density of TIM is correlated with the N stage and TNM stage of colorectal cancer,and it is an independent predictor of poor survival for patients with colorectal cancer.

Objective To analyze the clinicopathological factors on the prognosis and investigate the necessity of adjuvant chemotherapy for patients with stage Ⅱ colorectal cancer.Methods The clinical data of 255 patients with stage Ⅱ colorectal cancer who were admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2000 to December 2005 were collected.The survival curve was drawn by Kaplan-Meier method,and the survival rate of the patients were analyzed by Log-rank test.Factors influencing the survival were analyzed by Cox regression model.Results All patients were followed up till April 23,2010,and the mean time of follow-up was (63 ± 22)months.The median survival time was 63 months.The 5-year and tumor-free survival rates were 85.3％ and 83.7％,respectively.The 5-year overall and tumor-free survival rates of patients without preoperative bowel obstruction or perforation were 86.9％ and 85.6％,which were sigaificantly higher than 72.7％and 68.4％ of patients with preoperative bowel obstruction or perforation(x2 =4.546,4.573,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates of patients with negative resection margin were 85.5％ and 83.9％,which were significantly higher than 75.0％ and 75.0％ of patients with positive resection margin(x2 =7.020,6.009,P ＜ 0.05 ).The result of multivariate analysis revealed that preoperative bowel obstruction or perforation were the independent risk factors for patients with stage Ⅱ colorectal cancer(Wald =4.477,relative risk =2.371,95 ％ confidence interval:1.066-5.275,P ＜ 0.05 ).The 5-year overall and tumor-free survival rates were 87.3％ and 86.0％ for patients who received adjuvant chemotherapy,and were 82.2％ and 80.3％ for patients who did not receive adjuvant chemotherapy (P ＞ 0.05 ).Conclusions Preoperative bowel obstruction or perforation are independent risk factors for the survival of patients with stage Ⅱ colorectal cancer.Adjuvant chemotherapy could not improve the prognosis of patients with stage Ⅱ colorectal cancer.

Objective: To review children′s primary ciliary dyskinesia (PCD) in the pathogenesis, clinical manifestation, diagnosis and treatment. Method: To summarize and analyze the clinical data of a patient who was admitted to the first affiliated hospital of Xiamen University with primary ciliary dyskinesia in April 2014 while referring to related literature. Result: An 11 years old boy, weighting about 22 kg, had a course of more than 10 years with repeated cough, stuffy and runny nose shortly after the birth. Examinations after admission to hospital showed that he presented with visible clubbing, bilateral paranasal sinus area tenderness, pharynx posterior wall with visible yellow pussy stuff drip and bilateral lung had scattered wet rales. Auxiliary examination revealed bilateral maxillary sinus, ethmoid sinus inflammation and bronchitis with left lower lung bronchiectasis. Fiberoptic bronchoscopy discovered congestion and a lot of sputum; ciliary biopsy pathology displayed that cilia were sparse and partial cilia 9+ 2 microtubules structural abnormalities. Full sequence of exon gene sequencing revealed two mutations located at chromosome 16 chr16: 71061369 (non-coding regions) and chr16: 70993591 (coding). Two novel mutations m. 3362A>G(E20) and c. 6101G>A(E39) in exon 16 of the HYDIN gene were identified. With the" ciliary motility disorder, gene" as keywords , the CNKI, Wanfang digital knowledge service platform and PubMed were searched for relevant articles from the establishment to July 2016. The studies retrieved included 9 cases and these cases were summarized. Comprehensive analysis showed that HYDIN gene mutations related PCD patients had the typical PCD performance such as repeatedly wet cough, sinusitis, bronchiectasis, and otitis media. The majority of patients have a history of acute respiratory distress syndrome in infancy and no visceral dislocation was not found. Most of the patients had no obvious structural abnormalities in cilia electron microscopic examination. Conclusion The PCD patients with HYDIN genes mutations have clinical manifestations such as sinusitis, otitis media, bronchiectasis but without transposition of viscera. Cilia structure can be normal under the electron microscopic examination in some of patients.

AIM: To investigate the effects of advanced glycation end products on activation of Smad signaling pathway and collagenⅠ synthesis in proximal tubular epithelial cells.METHODS: Advanced glycation end products(AGE-BSA) were prepared by incubation of bovine serum albumin(BSA) with D-glucose.Normal rat proximal tubular epithelial(NRK52E) cells were cultured in RPMI-1640 medium with AGE-BSA.Phosphorylation and nuclear translocation of Smad2/3 were examined by immunocytochemistry.Levels of TGF-?_1 in supernatant of cell culture were measured by enzyme-linked immunosorbent assay(ELISA).Expression of TGF-?_1,Smad2,Smad3 and Smad7 mRNA were detected by RT-PCR.Expression of ?-SMA,E-cadherin and collagenⅠproteins were detected by Western blotting.RESULTS: AGE-BSA induced Smad2/3 phosphorylation and nuclear translocation,two peaks occured at 30 min(68% vs 16%,P

Objective:To explore the relationship between metabolic acidosis and cardiac valve calcification in maintenance hemodialysis (MHD) patients in the Pearl River Delta Region.Methods:Patients on MHD greater than 3 months who were treated in 10 blood purification centers in the Pearl River Delta Region from July 1 to September 30, 2019 were selected for this multicenter cross-sectional study. Based on a Doppler ultrasound, MHD patients were further divided into non-valve calcification group and valve calcification group. The demographics data, frequency of dialysis, blood pressure, single pool Kt/V(spKt/V), dialysis medications and laboratory data were collected and compared. Spearman correlation analysis was used to analyze the correlation between serum carbon dioxide combining power (CO 2CP) and cardiac valve calcification. Multivariate logistic regression model was used to analyze the influencing factors of cardiac valve calcification. Results:A total of 664 MHD patients were included in this study, with age of (57.0±14.2) years old and dialysis age of 43.0 (22.3, 71.7) months, including 395 males (59.5%) and 269 females (40.5%). Among them, there were 119 patients (17.9%) with diabetes and 186 patients (28.0%) with dialysis 2 times per week. There were 329 patients (49.5%) in the valve calcification group, and 335 patients (50.5%) in the non-valve calcification group. Compared to those in non-valve calcification group, valve calcification group had longer duration of dialysis, higher proportion of patients with dialysis 2 times per week, higher levels of diastolic blood pressure, fasting blood glucose, intact parathyroid hormone and ferritin, higher proportion of patients with blood CO 2CP<19 mmol/L (median CO 2CP), higher proportion of patients on usage of calcium channel blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, α-receptor blocker, β-receptor blocker, calcitriol and lanthanum carbonate (all P<0.05), while the levels of spKt/V, hemoglobin, serum CO 2CP, corrected calcium, blood phosphorus, blood alkaline phosphatase, albumin, total cholesterol, triacylglycerol, low-density lipoprotein, high-density lipoprotein, transferrin saturation, and the proportion of patients on usage of sevelamer and cinacalcet were lower (all P<0.05). Spearman analysis showed significant negative correlation between serum CO 2CP and valve calcification ( rs=-0.697, P<0.001). Multivariate logistic regression analysis showed that dialysis performed twice a week ( OR=2.789, 95% CI 1.232-6.305, P=0.014), blood total cholesterol ( OR=1.449, 95% CI 1.014-2.071, P=0.042), CO 2CP<19 mmol/L ( OR=22.412, 95% CI 10.640-47.210, P<0.001) were the influencing factor of valve calcification in MHD patients. Conclusions:MHD patients with cardiac valve calcification have significant acid loading. Metabolic acidosis is an independent influencing factor for cardiac valve calcification in MHD patients.

AIM: To observe the effect of antibiotic treatment on the inflammatory mediator expression in peritoneum and the peritoneal transport function in rats with acute peritonitis, and explore its mechanisms. METHODS: Eighty-six SD rats were randomly divided into three groups. Control group (n=28) were treated with PBS (ip), peritonitis group (n=28) and treatment group (n=28) were challenged with the E.coli (ip), but at 3 h and 9 h gentamicin was given (ip) in treatment group. Seven rats of every group were randomly sacrificed at 24 h, 48 h, 72 h and 7 d. Peritoneal equilibration test (PET) was did before they were killed. Leukocyte count, pathological changes and the expression of CD45, NF-?B, IL-1?, TNF-? in peritoneum were examined. RESULTS: (1)The blood leukocytes in peritonitis group decreased strikingly, but did not change obviously in other two groups. The peritoneal fluid leukocytes in peritonitis group increased significantly from 24 h to 72 h, while in treatment group, it enhanced more strikingly than peritonitis group at 24 h, and recovered earlier. (2) Both in peritonitis group and treatment group, the expression of activated NF-?B, IL-1?, TNF-? and CD45 increased significantly, but the treatment group was lower than model group at 48 h and 72 h. The mRNA level of IL-1? and TNF-? had the same trend as their protein expression. (3) Compared with the control group, UF and D/D_0 Glu decreased significantly in model group and treatment group, and D/PTP increased dramatically. The D/P TP in treatment group lowered obviously compared with peritonitis group, while the net UF and D/D_0 Glu had not significant difference between treatment group and model group. CONCLUSION: Antibiotic treatment can partly decrease the expression of inflammatory mediators in peritoneum of rats with acute peritonitis and also can improve the protein transport ability to some extent, but can not improve the peritoneal ultrafiltration and the glucose transport function.