OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7 ± 15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2％. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95％CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95％CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95％CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95％CI 1.72-26.82, P=0.006) between pre - CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95％CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95％CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95％CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95％CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95％CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95％ CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality.

Objective    To evaluate the strategy of chemoradiotherapy following endoscopic R0 resection for esophageal cancer in M3-T1b stage. Methods    There were 45 esophageal cancer patients with M3-T1b stage with endoscopic R0 resection followed by additional chemoradiotherapy from ECETC (Esophageal Cancer Endoscopic Therapy Consortium) as a trial group with 34 males and 11 females at age of 61.37±7.14 years. There were 90 patients with esophagectomy from Fudan University Shanghai Cancer Center as a control group with 63 males and 27 females at age of 61.04±8.17 years. Propensity score match (1:2) was used to balance the factors: gender, age, position, depth of invasion and lymphovascular invasion (LVI), which may influence the outcomes. Overall survival (OS) rate, relapse free survival (RFS) rate, and local recurrence rate were compared between the two groups. Result    There was no statistical difference (HR=2.66 with 95%CI 0.87 to 8.11, P=0.179) in terms of OS rate between the two groups. One, two and three years overall survival rate of patients in the control group was 93%, 86%, and 84%, respectively. Nobody died in the trial group within 3 years after surgery. The RFS rate between the two groups didn’t significantly differ (HR=1.48, 95% CI 0.66 to 3.33, P=0.389). One, two and three years RFS rate of patients in the contorl group was 87%, 78%, and 76%, respectively, while 97%, 93%, and 73% in the trial group, respectively. The local recurrence rates between the two groups didn’t significantly differ either ( HR=0.53，95%CI 0.13 to 2.18, P=0.314). One, two and three years local recurrence rate of patients in the control group was 5%, 6% and 6%, respectively, while 0%, 0% and 21% in the trial group, respectively. Conclusion    Similar outcomes are found regarding OS, RFS and local recurrence rates between the two groups. The strategy of endoscopic R0 resection followed by additional chemoradiotherapy has prospect for the treatment of esophageal cancer in M3-T1b stage. And this kind of therapy may be provided for those with risk factors or can not tolerate surgery.

Objective: To explore the gender-specific risk factors of new-onset cerebral hemorrhage. Methods: In this prospective cohort study,a total of 98 961 participants((51.1±12.6)years old), who underwent the 2006 to 2007 physical examination and met the inclusion criteria, were enrolled from the Kailuanstudy cohort. There were 78 908 (79.7%) male,and 20 053 (20.3%) female.The incidence of cerebral hemorrhage was observed once per year until December 31, 2016.The difference on the incidence of cerebral hemorrhage between male and female was compared. Multivariate Cox regression analysis was applied to analyze therisk factors of cerebral hemorrhage events among different genders. Results: The participants were followed up for(10.00±0.73) years,and 860 cerebral hemorrhage events were recorded during follow up. The incidence of cerebral hemorrhage in the population was 86.90/10 million person years (standardized incidence rate of 47.85/10 million person years). The incidence of cerebral hemorrhage was significantly higher in male (49.61/10 million person years) than in female (34.07/10 million person years, P<0.05). Multivariate Cox regression analysis showed that 45-59 years old, ≥ 60 years old, diabetes,and waist-hip ratio were more strongly related to new-onset of cerebral hemorrhage events in female than in male, and the hazard ratios(95%CI) were 2.33 (1.23-4.43) ,2.71 (1.30-5.66) ,2.16 (1.24-3.74) and 8.79 (1.42-54.32) in female versus 1.55 (1.21-1.97) ,2.16 (1.68-2.78) ,1.19 (0.93-1.53) and 3.21 (1.09-9.41) in male, respectively. The risk of male cerebral hemorrhage increased by 29% (HR=1.29, 95%CI 1.19-1.40) in male and 24% (HR=1.24, 95%CI 1.20-1.28) in female,when the systolic blood pressure increased 10 mmHg (1 mmHg=0.133 kPa). Conclusions: The incidence of cerebral hemorrhage is higher in male than in female in this cohort.The association between systolic blood pressure and cerebral hemorrhage is stronger in male than that in female.The associations between age, waist-hip ratio, diabetes and cerebral hemorrhage are stronger in female than in male. Trial Registration Chinese Clinical Trail Registry, ChiCTR-TNC-11001489.

Objective To investigate the effect of calcitriol soft capsules and telmisartan tablets for the treatment of early diabetic nephropathy.Methods 80 cases of early diabetic nephropathy in 254 hospital of Chinese people's liberation army were selected.According to the treatment methods,they were divided into the conventional medication group(40 cases,Telmisartan Tablets were used)and the combined medication group(40 cases,telmisartan tablets combined with calcitriol soft capsules were used).The therapeutic effects in the two groups were compared.Results In the combined group,renal function improved significantly better than that in the control group(P<0.05).The total effective rate in the combined medication group is higher than that in the conventional group(P< 0.05).Conclusion the treatment of and It was effective which calcitriol soft capsules combined with telmisartan tablets on the treatment in the early stage of diabetic nephropathy,it can improve renal function and delay the disease progression.

Objective To investigate the clinic effect of tunnel technique on endoscopic submucosal dissection(ESD)for massive colorectal laterally spreading tumor(LST). Methods A retrospective study was conducted on the data of patients with colorectal large area LST(the shortest diameter>4 cm) undergoing ESD by tunnel technique from January 2015 to June 2016 in Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine. The size of resected specimens, operation time, complications, pathology results, the number of en bloc resection and curative resection were analyzed. Results A total of 14 cases were collected, including 7 males and 7 females. The longest diameters of resected specimens were from 4.0 to 7.0 cm with mean size of 5.18 ± 0.49 cm. The operation times were from 40 to 120 min with mean time of 63.57±12.95 min. Intraoperative perforation occurred in 2 cases but no delayed perforation and bleeding occurred. Postoperative pathology showed 1 patient with adenoma hyperplasia with crypt abscess,3 patients with low grade intraepithelial neoplasia,6 patients with high grade intraepithelial neophasia,1 patient with carcinoma in situ, 1 patient with carcinoma in M3, and 2 patients with carcinoma in SM1. The number of cases who received en bloc resection, complete resection, and curative resection were 13, 13, and 13, respectively. Conclusion ESD by tunnel technique is safe and effective in the treatment of colorectal large area LST,which is worth popularizing in clinics.

Objective:To analyze the 3D changes of pharyngeal airway in patients with skeletal Class Ⅲ malocclusion after rapid maxillary expansion(RME)and maxillary protraction.Methods:53 patients underwent orthodontic treatment with Hyrax palatal ex-panders and maxillary protraction.Cone-Beam computed tomography(CBCT)scan was taken before treatment(T0),after 1 6 d RME (T1 )and after about 5 month maxillary protraction(T2).Data were reconstructed into 3D model,sagittal and transversal measure-ments,cross sectional areas,volumes of the pharyngeal airway were computed.Results:After RME,the transversal measurements, cross sectional areas,volumes of nasal passage were increased(P <0.05).After maxillary protraction,the 4 nasopharyngeal measure-ments were increased(P <0.05).Conclusion:RME and maxillary protraction may increase pharyngonasal airway.

Objective To evaluate the short-term and long-term effects of pharyngeal airway in mandibular prognathism patients after the combined orthodontic and orthognathic treatment.Methods The sample included 28 skeletal Class Ⅲ patients (13 males,15 females) who had undergone mandibular setback surgery and orthodontic treatment.Cone-beam CT was taken one week before treatment (T0),6 months (T1) and 3 years after surgery (T2).Raw data were reconstructed into three-dimensional model.Sagittal and transversal measurements,cross sectional areas,partial and total volumes were computed.Results Six months after surgery,oropharyngeal volume [(9 021±4 263) mm3],hypopharyngeal volume [(9 236±5 963) mm3] and total volume [(28 619±9 854) mm3] decreased significantly (P＜0.05).Three years after surgery,only sagittal diameters [(15.9±3.5) mm] and cross sectional areas [(996±398) mm2] in the first cervical vertebra plane came back to the original levels (P＞0.05).Conclusions The pharyngeal airway space decreased after orthodontic-orthognathic therapy in the short term and it increased in some areas in the long term.

Objective To assess the values of color Doppler and magnetic resonance imaging (MRI) in the identification of cervical lymph node micrometastasis of tongue cancer.Methods Totally 96 cases of tongue cancer with impalpable neck lymph node was examined with color Doppler and MRI within one week before surgery.Chi-square test was used to assess if the presence of regional lymph node micrometastasis,histopathological analysis as a golden standard lymph node micrometastasis.Results For the diagnosis of cervical lymph node micrometastasis,color Doppler was significantly better than MRI in sensitivity (72.5％ vs 50.0％,P=0.039) and the accuracy (78.1％ vs 64.6％,P =0.038),but no significant difference in the specificity (82.1％ vs 75.0％,P =0.357),the positive predictive value (74.4％ vs 58.8％,P =0.159) and the negative predictive value (80.7％ vs 67.7％,P =0.108).Conclusion Color Doppler is better than MRI in the sensitivity and accuracy for the diagnosis of cervical lymph node micrometastasis of tongue cancer.