[BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene].

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

[Prognostic value of perioperative change of neutrophil elastase and myeloperoxidase in coronary circulation on perioperative myocardial injury and clinical outcome of patients underwent surgical valve replacement].

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 µg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) µg/L vs. (447.2±135.9) µg/L, P<0.01) and NE ((417.0±83.1)µg/L vs. (341.0±68.3)µg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.

The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis.

PURPOSE: The purpose of this study is to evaluate the effectiveness and safety of liraglutide/liraglutide + metformin in overweight/obese women with polycystic ovary syndrome (PCOS). METHODS: The related literatures published until April 2021 were searched in PubMed, Cochrane Library, MEDLINE and EmBase. RESULTS: Six randomized controlled trials of 127 related articles were obtained through searching. Three articles compared liraglutide with metformin, and four articles compared liraglutide combined with metformin with metformin. Our meta-analysis suggests that liraglutide was superior to metformin only in weight loss [MD = - 2.74, 95% CI (- 4.29, - 1.18), P = 0.0006]. Compared with metformin group, the combination group had significant advantages in weight loss [MD = - 3.81, 95% CI (- 5.16, - 2.46), P < 0.001], BMI [MD = - 2.59, 95% CI (- 3.12, - 2.07), P < 0.001], waist circumference [MD = - 6.26, 95% CI (- 7.79, - 4.72), P < 0.001], fasting blood glucose [MD = - 0.59, 95% CI (- 0.74, - 0.44), P < 0.001] and fasting insulin [MD = - 1.52, 95% CI (- 2.69, - 0.35), P = 0.01], while the incidence of adverse reactions was relatively high [RR = 2.91, 95% CI (1.55, 5.46), P = 0.00009]. CONCLUSION: The present results indicate that liraglutide and metformin have the similar effects in the treatment of overweight/obese PCOS patients. Liraglutide combined with metformin is more effective than metformin in improving PCOS, but it is necessary to master the correct medication method to reduce the occurrence of adverse reactions.

[Correlation between cerebral oxygen saturation monitored by near-infrared spectroscopy during operation and risk of stroke after acute type A aortic dissection surgery].

Objective: Near-infrared spectroscopy (NIRS) is widely used for intraoperative cerebral oxygen saturation monitoring in patients with acute type A aortic dissection. This study aimed to investigate the correlation between NIRS-derived oxygen saturation and risk of postoperative stroke. Methods: This study included 193 patients with acute type A aortic dissection undergoing emergency surgery and elective unilateral cerebral perfusion via the right axillary artery at the Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing, China, from 2018 to 2020. NIRS was used for intraoperative cerebral oxygen saturation monitoring, and the basal values and the lowest values of cerebral oxygen saturation during deep hypothermic circulatory arrest (DHCA) were recorded. The patients were divided into no-stroke group (n=178, 92.2%) and stroke group (n=15, 7.8%) according to the absence or presence of postoperative stroke. The differences in preoperative, operative and postoperative clinical differences between the two groups were compared, and the relationship between the lowest cerebral oxygen saturation value and the change in cerebral oxygen saturation value ((base-lowest)/basal) and postoperative stroke were analyzed. Results: The proportion of preoperative atrial fibrillation (6.7% vs. 0.6%, P=0.026), and the proportion of preoperative hypotension (26.7% vs. 9.0%, P=0.031) were significantly higher in the stroke group than no-stroke group. There were no differences in the surgical approach between the two groups. Cardiopulmonary bypass (CPB) time ((256.1±84.8) h vs.(217.8±58.4) h, P=0.020), postoperative mechanical ventilation time ((139.3±172.8) h vs. (35.6±45.6) h, P<0.001) were significantly longer in stroke group as compared to no-stroke group. Incidence of postoperative tracheotomy (20.0% vs. 1.1%, P<0.001), acute kidney injury (73.3% vs. 30.3%, P=0.001) and continuous renal replacement therapy (46.7% vs. 11.8%, P<0.001) as well as mortality (20.0% vs. 5.1%, P=0.022) were significantly higher in the stroke group than in non-stroke group. There was no significant difference in the basal NIRS value and the lowest NIRS value during DHCA between the two groups. Patients in the stroke group had a significantly greater intraoperative change rate of right NIRS as compared to no-stroke group (15.2%±15.7% vs. 9.2%±7.0%, P=0.006). Conclusions: NIRS is valuable for monitoring cerebral oxygen saturation during acute type A aortic dissection surgery, and the rate change of NIRS during operation correlates significantly with postoperative stroke.

[Ultrastructural features of the corneal epithelium with micromolecular compound J2 in the corneal allograft of rats using atomic force microscopy].

Objective: To study the ultrastructural features of the corneal epithelium in the corneal allograft of rats with micromolecular compound J2. Methods: An experimental study. Primarily cultured corneal epithelial cells of rats were used. Mononuclear cells (MNCs) by density gradient centrifugation were assigned into the experimental group [MNCs (2 ml)+corneal epithelial cells+J2], control group [MNCs (2 ml)+corneal epithelial cells] and blank group (corneal epithelial cells). Quantity of CD80 expression was obtained by flow cytometry after coculture. Amplitude and height images were obtained by tapping mode atomic force microscopy (AFM) with a scan rate of 2 Hz and an integral gain of 0.3 to 0.5. Statistical analysis of Ra, Rq, Rvm and Rt was performed using the single-factor analysis of variance, and P value was calculated. Results: There were obvious differences in the ultrastructure measured by AFM among groups. Ra was 86.75±12.60 in the experimental group, 120.23±12.11 in the control group, and 61.94±10.62 in the blank group (F=306.92, P<0.01). Rq was 102.53±9.45, 138.30±10.13, and 91.96±7.25, respectively, in the three groups (F=361.85, P<0.01). Rvm was -42.21±14.22, -67.36±10.89, and -32.18±19.01, respectively (F=72.22, P<0.01). Rt was 437.32±15.66, 495.32±13.96, and 339.92±11.22, respectively (F=1634.26, P<0.01). The one way analysis of variance showed significant differences in these parameters among groups. Conclusions: Corneal epithelial cells of rats activated by MNCs had higher CD80 expression, but the expression became decreased with micromolecular compound J2. The ultrastructure of the corneal epithelium became coarser after MNCs activation, and the number of protrusions increased significantly. The ultrastructural changes were alleviated by J2.(Chin J Ophthalmol, 2021, 57: 608-613).

Prevalence and factors associated with motoric cognitive risk syndrome in community-dwelling older Chinese: a cross-sectional study.

BACKGROUND AND PURPOSE: A recently proposed pre-dementia syndrome, motoric cognitive risk (MCR) syndrome, is characterized by cognitive complaints and slow gait, and increases the risk of dementia and mortality. The aim of the present study was to explore the prevalence of and factors associated with MCR syndrome in elderly community-dwelling Chinese subjects. METHODS: The Ningbo Community Study on Aging recruited 953 Chinese community-dwelling participants aged ≥ 65 years from November 2016 to March 2017. Handgrip, Five-Times-Sit-to-Stand (FTSS) test time and body composition, as well as comprehensive geriatric evaluation, were measured as potentially independent factors associated with MCR syndrome. RESULTS: The prevalence of MCR syndrome was 12.8% in men and 12.6% in women, and high prevalence of MCR syndrome was not associated with age or sex. Multiple logistic regression analysis by sex showed that a 1-SD increase in FTSS test time in males and females was associated with 45% (95% confidence intervals, 19-76; P < 0.01) and 20% (95% confidence intervals, 9-33; P < 0.01) higher risk of having MCR syndrome, respectively, whereas handgrip strength was inversely correlated with MCR syndrome in males [odds ratio (OR), 0.91; P = 0.02] but not females (P = 0.06). Moreover, the relationship of arm fat mass and MCR syndrome was statistically significant in both sexes (OR, 1.69-1.77), but leg fat mass was only associated with MCR syndrome (OR, 1.56; P = 0.02) in men. CONCLUSIONS: Handgrip, FTSS test time and body composition were associated in a sex-specific manner with MCR syndrome in elderly community-dwelling Chinese subjects. Our results on MCR syndrome are novel and should be considered as important information in future studies.

[The incidence and related factors of coronary events among 40-49 years old patients undergoing cardiac thoracotomy without preoperative CAG].

Objective: To investigate the long-term incidence of coronary events and related factors in patients undergoing cardiac thoracotomy without preoperative coronary angiography (CAG). Methods: This was a retrospective study. The clinical data of patients, aged between 40 and 49 years old, who underwent cardiothoracic surgery, including heart valve surgery, congenital heart disease surgery, cardio great vessels surgery and other non-coronary artery disease (CAD) surgery, in Nanjing Drum Tower Hospital from December 2009 to May 2017, were enrolled. Patients with suspected CAD, or patients with coronary CTA defined calcified coronary arteries received CAG examination prior operation, and the rest patients did not receive routine CAG examinations. The patients who did not receive routine CAG examinations were followed up by telephone. The primary endpoints include death related to coronary arteries, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI). The secondary endpoints include the new onset angina, clinically diagnosed CAD or receiving the first and second prevention for CAD. The other outcome events included cardiac death and all-cause mortality. The primary and secondary endpoints were all regarded as coronary events. The patients without preoperative CAG were divided into two groups: the positive group and the negative group, according to the incidence of coronary events during follow-up. Clinical data were compared between the two groups. Results: A total of 952 patients were included. The age was (45.2±2.7) years old, 406(42.65%) patients were male. Preoperative CAG was performed in 73 patients, among whom 9 (12.32%) patients underwent simultaneous CABG. Among the 879 cases who did not undergo coronary angiography before the operation, 18(2.05%) died during perioperative period (hospitalization and within 30 days after discharge). The patients were followed up for (61.6±25.8) months, and 28(3.25%) patients were lost to follow up. During long-term follow up, there were no fatal cases due to severe coronary events and no cases of CABG or PCI. Only 4.41% (38/861) patients had the secondary endpoints, namely the occasional onset of atypical angina. The incidence rate of the long-term coronary events, all-cause mortality and cardiac death were 4.41% (38/861), 1.16% (10/861), 0.46% (4/861) during long-term follow-up. The prevalence of hypertension was significantly higher in positive group than negative group (34.21% (13/38) vs. 20.89% (164/785), P=0.045). Conclusions: It is feasible not to perform preoperative CAG examination for non-CAD patients aged 40-49 years who will undergo cardiac thoracotomy. However, we need to be aware the risk of coronary events in the patients complicating with risk factors of CAD, such as hypertension.

Full Sibling Testing Based on NGS-SNP Genotyping Method and IBS Strategy.

ABSTRACT: Objective To evaluate the effectiveness of single nucleotide polymorphism （SNP） genoty-ping in combination with identity by state （IBS） strategy in full sibling testing. Methods Thirty-five blood samples were collected from a four-generation family. Ninety autosomal SNPs were genotyped using Precision ID Identity Panel. The distribution of IBS scores for full siblings and other relationships were calculated and compared. The relationships were determined using Fisher discriminant function and threshold method, respectively. Results Based on family members and previous research, 44, 30, 111, 71 and 1 000 pairs of full siblings （FS）, grandparent-grandchild （GG）, uncle/aunt-nephew/niece （UN）, first cousins （FC） and unrelated individuals （UI） were obtained, respectively. The average IBS scores were 148, 130, 132, 124 and 120, respectively. Except for the GG and UN pairs, the distribution differences among the other relationships had statistical significance （P<0.05）. The false rates of Fisher discriminant function to determine relationships were 1.3%, 22.3%, 17.0% and 38.7% for FS, GG, UN and FC, respectively. Based on the simulation data, the thresholds t1=128 and t2=141 were recommended to determine full sibling relationships （the false rate ≤0.05%）. Conclusion The 90 SNP genetic markers included in the Precision ID Identity Panel meet the testing requirements for full sibling relationships. The threshold method based on IBS has a relatively lower false rate and is more flexible.

[Treatment experience of cardiac rupture in patients with acute myocardial infarction].

Objective: To analyze the treatment results of cardiac rupture in patients with acute myocardial infarction (AMI) . Method: Clinical data of 6 with cardiac rupture after AMI, who were hospitalized in our hospital from June 2015 to June 2017, were retrospectively analyzed,and the clinical manifestations, methods of treatment and outcomes were investigated. Results: Cardiac function classification was Killip class Ⅱin all patients. There were 3 massive anterior wall myocardial infarction, 2 anterior wall myocardial infarction,and 1 inferior myocardial infarction. There were 4 patients with ventricular septal defect, 1 patient with rupture of papillary muscle,and 1 patient with left ventricular free wall rupture.All patients received continuous infusion of vasoactive medicines and treated with intra-aortic balloon pump(IABP), 2 patients (1 patient accepted operative treatment,and 1 patient received conservative treatment) were treated with extracorporeal membrane oxygenation (ECMO), mechanical ventilation,and continuous renal replacement therapy(CRRT).Three patients received surgical repair,1 case was supported by IABP, 1 case supported by ECMO,CRRT,and IABP,and 1 case did not use IABP or ECMO post operation. All 3 surgically treated patients recovered successfully and were discharged from hospital.Meanwhile, in the other 3 patients treated conservatively, 2 patients died in the hospital and 1 patient was discharged according to own will. Conclusion: On the basis of vasoactive medicines and IABP, surgery repair is a feasible option for cardiac rupture patients secondary to AMI,and ECMO may improve the perioperative state in these patients.

[Clinical analysis of different root treatment methods in acute Stanford type A aortic dissection].

Objective: To discuss the perioperative and follow-up results of different surgical methods for acute Stanford type A aortic dissection patients and analyzed the results. Methods: The clinic data of 351 acute Stanford type A aortic dissection patients received surgical therapy at Department of Thoracic and Cardiovascular Surgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital from January 2008 to December 2015 were analyzed retrospectively. There were 272 male and 79 female patients, aging from 22 to 83 years with a mean age of (52±13) years. According to root size, aortic valve structure and the status of dissection involvement, these patients were devided into three major groups: 218 cases with root reconstruction using Dacron felts, 34 cases with root reconstruction concomitant with aortic valve resuspension repair and 99 cases in with Bentall procedure. Proper shape based on the status of dissection involvement of Dacron patch was cut and put between the middle and outerlayer of aorta, then inside the inner layerone band Dacron felt was sutured with the aorta and the new middle layer with Dacron patch as mentioned above. In some cases the prolapsed aortic valve was re-suspended to the aortic cusp. Clinical outcomes among the 3 procedures were compared by χ(2) test, Fisher's exact test, t test and analysis of variance. Results: Cardiopulmonary bypass, cross-clamp, and circulatory arrest times of all the patients were (250±78), (171±70) and (31±10) minutes, respectively. The 30-day mortality was 9.2%(33/351), while no difference among the 3 procedures (9.6%, 8.8% and 9.1%). In the average follow-up time of (26.0±23.0) months (range from 0.5 to 90.0 months), survival rates were similar among the 3 procedures (77.7%, 77.4% and 77.8%). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (diameter of 50 mm). Conclusions: The indication of root management of acute Stanford type A aortic dissection is based on the diameter of aortic root, structure of aortic leaflets, and the dissection involvement. For most acute Stanford type A aortic dissection patients, aortic root reconstruction is a feasible and safe method.

[Analysis of the prevalence and risk factors of preoperative angiography confirmed coronary artery stenosis in patients with degenerative valvular heart disease].

Objective: To estimate the prevalence and the risk factors of preoperative coronary angiography (CAG) confirmed coronary stenosis in patients with degenerative valvular heart disease. Methods: A total of 491 patients who underwent screening CAG before valvular surgery due to degenerative valvular heart disease were enrolled from January 2011 to September 2014 in our hospital, and clinical data were analyzed. According to CAG results, patients were divided into positive CAG result (PCAG) group or negative CAG (NCAG) group. Positive CAG result was defined as stenosis ≥50% of the diameter of the left main coronary artery or stenosis ≥70% of the diameter of left anterior descending, left circumflex artery, and right coronary artery.Risk factors of positive CAG result were analyzed by multivariable logistic regression analysis, and Bootstrap method was used to verify the results. Results: There were 47(9.57%)degenerative valvular heart disease patients with PCAG. Patients were older ((68.0±7.6)years vs.(62.6±7.1)years, P<0.001) and the prevalence of typical angina was significantly higher (14.89%(7/47)vs. 2.03%(9/444), P<0.001)in PCAG group than in NCAG group. Multivariable logistic regression analysis showed that age (OR=1.118, 95%CI 1.067-1.172, P<0.001), typical angina (OR=8.970, 95%CI 2.963-27.154, P<0.001), and serum concentration of apolipoprotein B (OR=20.311, 95%CI 4.774-86.416, P<0.001) were the independent risk factors of PCAG in degenerative valvular heart disease patients. Bootstrap method revealed satisfactory repeatability of multivariable logistic regression analysis results (age: OR=1.118, 95%CI 1.068-1.178, P=0.001; typical angina: OR=8.970, 95%CI 2.338-35.891, P=0.001; serum concentration of apolipoprotein B: OR=20.311, 95%CI 4.639-91.977, P=0.001). Conclusions: A low prevalence of PCAG before valvular surgery is observed in degenerative valvular heart disease patients in this patient cohort. Age, typical angina, and serum concentration of apolipoprotein B are independent risk factors of PCAG in this patient cohort.

[Expression profiles and clinical implication of plasma chemokines in patients with Stanford type A aortic dissection].

Objective: To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD). Methods: We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients). Four plasma samples from AD patients and 4 plasma samples from healthy subjects were collected randomly with random numbers table, and the levels of different chemokines were examined by protein array analysis. Then, plasma levels of chemokines including macrophage inflammatory protein 1ß(MIP-1ß), epithelial neutrophil activating peptide 78(ENA-78), interleukin 16(IL-16), interferon inducible protein 10(IP-10) and FMS-like tyrosine kinase 3(Flt-3) ligand were analyzed by luminex. Pearson analysis was used to determine the correlations between the chemokines and serum C reactive protein (CRP) levels. Results: Plasma levels of MIP-1ß(34.0(29.3, 47.2) ng/L vs. 51.0(28.2, 80.7) ng/L, P<0.05) and ENA-78(110.5(59.1, 161.4) ng/L vs. 475.7(299.3, 837.3) ng/L, P<0.05) were significantly lower in H-AD group, while plasma IL-16 level was significantly higher in H-AD group(54.7(16.3, 187.8) ng/L vs. 17.5(11.9, 20.8) ng/L, P<0.05) than in H-CON group. Plasma levels of MIP-1ß(48.3(26.4, 62.1) ng/L, P<0.05) were significantly lower in H-AD patients than in NH-AD patients. Plasma level of ENA-78 was significantly lower in NH-AD group than in NH-CON group (95.0(58.0, 155.0) ng/L vs. 257.7(85.2, 397.8) ng/L, P<0.05). The levels of IP-10 and Flt-3 ligand were similar among the 4 groups (all P>0.05). Pearson analysis showed that there were no correlation between MIP-1ß(r(2)=0.01, P>0.05), ENA-78(r(2)=0.02, P>0.05), IL-16(r(2)=0.02, P>0.05), IP-10(r(2)=0.00, P>0.05), Flt-3 ligand(r(2)=0.02, P>0.05) and CRP levels in patients with Stanford type A aortic dissection. Conclusions: Lower plasma levels of MIP-1ß and ENA-78 and higher plasma levels of IL-16 may associate with the occurrence and development of type A aortic dissection, but their concentrations are not correlated with serum CRP levels. There is no significant change on plasma levels of IP-10 and Flt-3 in the Stanford type A aortic dissection patients.

[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].

OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

Expression and variation of Myf5 and MyoD1 genes in different tissues of Wuzhishan pigs.

The myogenic regulatory factor (MRF) family includes Myf5, MyoD1, Myf4, and Mfy6 genes. This experiment assessed the variation of Myf5 and MyoD1 genes from birth to maturity (30, 210, and 360 days) in the back muscle tissue of Wuzhishan pigs (WZSP), and the expression of Myf5 and MyoD1 mRNA in the heart, liver, lung, spleen, kidney, muscle, stomach, and intestine tissues were also examined. The results indicate that the expression level of mRNA for Myf5 and MyoD1 genes in the back muscle tissue is directly proportional to age (P < 0.05). Furthermore, of the eight adult pig tissue types that were tested, the expression of Myf5 and MyoD1 was highest in the muscle tissue.

GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation.

(1)H magnetic resonance spectroscopy ((1)H MRS) and spectral editing methods, such as MEGA-PRESS, allow researchers to investigate metabolite and neurotransmitter concentrations in-vivo. Here we address the utilization of (1)H MRS for the investigation of GABA concentrations in the ASD brain, in three locations; motor, visual and auditory areas. An initial repeatability study (5 subjects, 5 repeated measures separated by ~5days on average) indicated no significant effect of reference metabolite choice on GABA quantitation (p>0.6). Coefficients of variation for GABA+/NAA, GABA+/Cr and GABA+/Glx were all of the order of 9-11%. Based on these findings, we investigated creatine-normalized GABA+ ratios (GABA+/Cr) in a group of (N=17) children with autism spectrum disorder (ASD) and (N=17) typically developing children (TD) for Motor, Auditory and Visual regions of interest (ROIs). Linear regression analysis of gray matter (GM) volume changes (known to occur with development) revealed a significant decrease of GM volume with Age for Motor (F(1,30)=17.92; p<0.001) and Visual F(1,16)=14.41; p<0.005 but not the Auditory ROI (p=0.55). Inspection of GABA+/Cr changes with Age revealed a marginally significant change for the Motor ROI only (F(1,30)=4.11; p=0.054). Subsequent analyses were thus conducted for each ROI separately using Age and GM volume as covariates. No group differences in GABA+/Cr were observed for the Visual ROI between TD vs. ASD children. However, the Motor and Auditory ROI showed significantly reduced GABA+/Cr in ASD (Motor p<0.05; Auditory p<0.01). The mean deficiency in GABA+/Cr from the Motor ROI was approximately 11% and Auditory ROI was approximately 22%. Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas.

Highly efficient beamline and spectrometer for inelastic soft X-ray scattering at high resolution.

The design, construction and commissioning of a beamline and spectrometer for inelastic soft X-ray scattering at high resolution in a highly efficient system are presented. Based on the energy-compensation principle of grating dispersion, the design of the monochromator-spectrometer system greatly enhances the efficiency of measurement of inelastic soft X-rays scattering. Comprising two bendable gratings, the set-up effectively diminishes the defocus and coma aberrations. At commissioning, this system showed results of spin-flip, d-d and charge-transfer excitations of NiO. These results are consistent with published results but exhibit improved spectral resolution and increased efficiency of measurement. The best energy resolution of the set-up in terms of full width at half-maximum is 108 meV at an incident photon energy tuned about the Ni L3-edge.

Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome.

Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents.

Association study of vascular endothelial growth factor gene polymorphisms with ectopic pregnancy in Chinese women.

OBJECTIVE: The purpose of this study is to evaluate potential associations between vascular endothelial growth factor (VEGF) gene polymorphisms and ectopic pregnancy (EP) in Chinese women. MATERIALS AND METHODS: This was a case-control study wherein 192 women with a history of EP were compared to 210 post-menopausal controls with two pregnancies and no EP for the genotyping of VEGF polymorphisms. Genotyping of the VEGF gene polymorphisms at -460C/T, -1 154G/A, -2578C/A and +936C/T were performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No significant differences were found in genotype and allele distributions of the -460C/T, +936C/T polymorphisms between cases and controls. Compared with the -1154G/G genotype, the -1154(A/A+G/A) genotype could significantly reduce the risk of developing EP. For the -2578C/A polymorphism, the A/A+C/A geno- type could significantly decrease the risk of developing EP, compared with the C/C genotype. The haplotype analysis suggested that the TAA (VEGF -460/-1154/-2578) and CAA haplotypes could significantly decrease the risk of developing EP compared with the haplotype of TGC. CONCLUSION: The -1154A or -2578A alleles of VEGF gene could significantly decrease the risk of EP and might be po- tentially protective factors for EP development in Chinese women.

[Clinical phenotypic and genotypic analysis of 5 pediatric patients with ß-ketothiolase deficiency].

Objective: To summarize the clinical and genetic characteristics of children with ß-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 µmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: ß-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of ß-ketothiolase deficiency.

[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.