Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.
COVID-19 ; Consensus ; Humans ; Oral Health ; Oral Medicine

Objective To investigate the population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province. Methods Rodents were captured using the mouse trap method in pastures from Batang Township and Longbao Township of Yushu City, Qinghai Province on May, August and October, 2018. The body weight and snout-vent length of all captured rodents were measured, and the species was identified according to the rodent morphology. Genomic DNA was extracted from rodent liver specimens and lesion specimens, and the mitochondrial cox1 gene of Echinococcus was amplified using PCR assay for identification of parasite species. In addition, the tissue specimens positive for PCR assay were sampled for pathological examinations. The prevalence of Echinococcus infections was estimated in rodents, and a phylogenetic tree was created based on Echinococcus cox1 gene sequences. Results A total of 285 small rodents were captured, including 143 Ochotona curzoniae (50.2%), 141 Lasiopodomys fuscus (49.5%), and 1 Neodon irene (0.3%), and there was a remarkable variation in habitat selection among these three rodent species. The number of L. fuscus correlated positively with vegetation coverage (r = 0.350, P = 0.264), with the greatest number seen in August, and the number of O. curzoniae negatively with vegetation coverage (r = −0.371, P = 0.235), with the highest number seen in August and the lowest number in May. The female/male ratios of O. curzoniae and voles were 1:0.96 and 0.82:1, respectively. The body weight (r = 0.519, P < 0.01) and snout-vent length (r = 0.578, P < 0.01) of O. curzoniae showed a tendency towards a rise with month, while the body weight (r = −0.401, P < 0.01) and snout-vent length (r = −0.570, P < 0.01) of voles presented a tendency towards a reduction with month. No Echinococcus infection was detected in voles, while 2.1% prevalence of E. shiquicus infection was seen in O. curzoniae. Phylogenetic analysis revealed consistent sequences of cox1 gene from E. shiquicus in Yushu City of Qinghai Province and Shiqu County, Ganzi Tibetan Autonomous Prefecture of Sichuan Province. Conclusions The small rodents around the human settlement in Yushu City of Qinghai Province mainly include O. curzoniae and L. fuscus, with the greatest numbers seen in May and August, respectively. Following the concerted efforts for echinococcosis control, the prevalence of Echinococcus infections is low in small rodents around the human settlement in Yushu City; however, there is still a risk of echinococcosis transmission.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in 7 family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 (0-12) days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusion The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

Objective:To compare the cuff pressure and leakage volume and the related complications of filling the tracheal tube cuff by minimum air leakage method and cuff pressure manometer method after endotracheal intubation, so as to provide theoretical basis for patients who was intubated to obtain appropriate cuff pressure.Methods:A prospective randomized controlled study was conducted. 100 patients admitted to the department of critical care medicine of the Fifth Center Hospital in Tianjin from December 2015 to June 2019 were enrolled. According to the random number table method, the patients were divided into the experimental group and control group, with 50 patients in each group. After successful endotracheal intubation, all patients were placed in a supine position with the head of the bed raised by 30°. The experimental group used the minimum air leakage method, and used the cuff pressure manometer to obtain the cuff pressure. In the control group, cuff pressure was maintained at 25-30 cmH 2O (1 cmH 2O = 0.098 kPa). Parameters such as cuff pressure and ventilator leakage volume at the beginning and 4 hours, 8 hours after the inflation were compared between the two groups, as well as the incidence of ventilation-associated pneumonia (VAP) and airway complications after extubation. Results:Among the 100 cases, 53 were males and 47 were females. The age ranged from 23 to 87 years old, with an average of (68.53±8.46) years old. The intubation time ranged from 1 to 16 days.① At 4 hours and 8 hours after inflation, the cuff pressures of the two groups were lower than that of the first time of inflation, and the air leakage of the ventilator increased gradually with the extension of time. Compared with the control group, cuff pressures at each time point in the experimental group were significantly higher than those in the control group [mmHg (1 mmHg = 0.133 kPa): 33.72±9.14 vs. 25.68±5.26 at 0 hour, 30.54±7.81 vs. 24.35±4.93 at 4 hours, 26.57±5.64 vs. 22.42±4.14 at 8 hours, all P < 0.05], and ventilator leakage volumes were smaller than those in the control group (mL: 25.57±8.51 vs. 34.65±9.47 at 0 hour, 40.54±8.51 vs. 60.34±7.85 at 4 hours, both P < 0.05). ② The incidence of VAP in the experimental group was significantly lower than that in the control group (4% vs. 10%, P < 0.05). There was no statistically significant difference in the incidence of other airway complications between the experimental group and control group (airway mucosal edema: 14% vs. 12%, ulcer: 8% vs. 6%, tracheal esophageal fistula: 0% vs. 0%, hoarseness: 4% vs. 6%, cough: 30% vs. 34%, sore throat: 28% vs. 32%, tracheal softening: 0% vs. 0%, cuff rupture: 10% vs. 8%, all P > 0.05). Conclusions:The optimal cuff pressure is very important for preventing VAP and reducing airway complications. The minimum air leakage method makes the clinical obtained endotracheal intubation cuff pressure more accurately, with less air leakage, safe and effective, and it is worthy of clinical promotion.

BACKGROUND: In the preliminary study, extracorporeal circulation system simulated physiological environment has been applied in limb preservation, significantly prolonging the severed limb preserving time. OBJECTIVE: To study the effect of enhancement-perfusion by extracorporeal circulation system on the blood supply of ischemic lower limbs. METHODS: Eighteen adult Bama mini pigs were equally randomized into three groups: group A (no intervention), groups B and C (establishing the ischemic model by arteria cruralis ligation at the right posterior lower limb). At 4 weeks after modeling, the model pigs in the group C received enhancement-perfusion therapy 1 hour per day. One week later, the situations of angiography were detected by digital radiography. The tibialis anterior separated from each pig was used to test the microvessel density by hematoxylin-eosin staining. The expression levels of vascular endothelial growth factor in the skeletal muscle and serum samples were monitored by western blot and ELISA, respectively. RESULTS AND CONCLUSION: Both diameter and distal collateral circulation of the arteria cruralis in the group C were much better than those in the group B. The microvessel density in the group C was significantly higher than that in the group B (P < 0.05), but the insignificant difference between groups A and C was found (P > 0.05). Both histionic and serum levels of vascular endothelial growth factor were significantly increased in the groups B and C compared with the group A, especially in the group C (P < 0.05). In summary, the enhancement-perfusion therapy by extracorporeal circulation system can considerably ameliorate blood supply of lower limbs, providing a promising method for treatment of ischemic lower limbs.

Objective To investigate the expression differences and significance of periostin (PN) in eyelid basal cell carcinoma associated fibroblasts (BCAFs) andnormal fibroblasts (NFs) after separation,culture,purification and identification.Methods The third generation of purified BCAFs and NFs was selected,and the concentrations of cell suspensions were modulated to 20 × 106 L-1 by trypsin,and then the cell suspension were seeded and cultured in 6-well plate by 2 mL per well.The cell culture supernatants were collected when BCAFs and NFs were cultured by serum-free medium for 48 h,then the content of PN in cell culture supernatants from BCAFs and NFs was detected by enzyme-linked immunosorbent assay (ELISA).The glass coverslips were placed at the bottom of the 6-well plate to make cell slides,and then the expression of PN in BCAFs and NFs cells were tested by immunofluorescence staining.Results ELISA showed that the content of PN in cell culture supernatants from BCAFs and NFs was (9.26 ± 2.35) μg · L-1 and (2.57 ± 0.41) μg · L-1.And the expression level of PN in BCAFs tested by immunofluorescence staining technology was higher than that in NFs cells,and the differences were statistically significant (all P ＜ 0.05).Conclusion The expression and secretion of PN in the eyelid BCAFs were highly enhanced when compared with NFs,suggesting that periostein may promote or inhibit the occurrence and development of the eyelid basal cell carcinoma in the microenvironment of the eyelid basal cell carcinoma.