Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To investigate the impacts of stroke volume variation (SVV)-guided goal-directed fluid therapy on intraoperative signs, intestinal barrier function and prognosis in patients undergoing laparoscopic radical rectal cancer surgery.Methods:A total of 90 patients who underwent laparoscopic radical resection for rectal cancer in Peking University International Hospital from May 2020 to May 2022 were prospectively selected as subjects, and divided into SVV group (45 cases) and traditional infusion group (45 cases) by random number table method. The SVV group was given SVV-guided goal-directed fluid therapy, and the traditional infusion group was given central venous pressure (CVP)-guided goal-directed fluid therapy. The operation-related indicators (urine volume, crystalloid volume, colloid volume, total fluid volume, blood loss and operation time), intraoperative signs indicators[heart rate (HR), CVP, mean arterial pressure (MAP)], intestinal barrier function indicators [diamine oxidase (DAO), D-lactic acid], inflammatory factor levels [interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and the incidence of complications were compared between the two groups.Results:There was no significant difference in the urine volume, blood loss and operation time between the two groups (all P>0.05), while the crystalloid volume, colloid volume and total fluid volume in the SVV group were greatly lower than those in the traditional infusion group (all P<0.05). There was no significant difference in HR between the two groups at different time points ( P>0.05). Compared with T 0, CVP at T 1 in the two groups was significantly decreased (all P<0.05), and increased at T 2 and T 3 compared with T 1 (all P<0.05). There was no significant difference in MAP at different time points in the SVV group (all P>0.05). The MAP at T 1, T 2 and T 3 in the traditional infusion group was significantly lower than that at T 0 (all P<0.05), and the MAP at T 1, T 2 and T 3 in the SVV group was significantly higher than that in the traditional infusion group (all P<0.05). Compared with T 0, DAO and D-lactic acid levels were significantly increased at T 1, T 3, T 4 and T 5 in the two groups (all P<0.05), and DAO and D-lactic acid levels at T 1, T 3, T 4 and T 5 in the SVV group were significantly lower than those in the traditional infusion group (all P<0.05). Compared with T 0, serum IL-10 level in the two groups was significantly decreased at T 4 ( P<0.05), and serum IL-6 and TNF-α levels were significantly increased at T 4 (all P<0.05). The serum levels of IL-10, IL-6 and TNF-α in the SVV group at T 4 were significantly different from those in the traditional infusion group (all P<0.05). Compared with T 4, the serum levels of IL-10 at T 5 were significantly increased (all P<0.05), while the levels of IL-6 and TNF-α were significantly decreased (all P<0.05), but there was no statistical significance between the two groups (all P>0.05). The incidence of postoperative infection, anastomotic fistula, vomiting and nausea in SVV group (13.33%) was significantly lower than that in traditional infusion group (35.33%) ( P<0.05). Conclusions:SVV-guided goal-directed fluid therapy for patients undergoing laparoscopic radical rectal cancer can effectively stabilize intraoperative vital signs, reduce inflammation, improve intestinal barrier function, and improve prognosis.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Objective:To investigate the risk factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau.Methods:From March 2019 to June 2020, prospective design was used to collect data of Qinghai-Tibet Plateau hypertension patients who were eligible for continuous enrollment in the Department of Cardiovascular Medicine in Hospital of Chengdu Office of People's Government of Tibet Autonomous Region. Questionnaire survey, physical examination and blood pressure measurement were performed on the selected patients. Fasting venous blood samples were collected for liver function test, blood lipid test, blood glucose test, and hemoglobin test, etc. Three times of morning urine samples were taken on different days, and urine protein creatinine ratio (UACR) was measured, UACR < 30 mg/g was negative for urinary protein, and UACR≥30 mg/g was positive for urinary protein. At the same time, the selected patients were examined by carotid artery color ultrasound and heart color ultrasound. The risk factors of proteinuria were analyzed.Results:A total of 588 patients with hypertension met the inclusion criteria, including 472 patients (80.3%) who received antihypertensive drug therapy, 239 patients (40.6%) had antihypertensive treatment compliance, and 252 patients (42.9%) reached the standard blood pressure after theropy. Hypertension was associated with diabetes mellitus in 150 patients (25.5%), and urinary protein was positive in 126 patients (21.4%). In univariate analysis, ethnic composition, systolic blood pressure [(138.19 ± 19.65) vs (133.16 ± 18.45) mmHg, 1 mmHg = 0.133 kPa], diastolic blood pressure [(85.80 ± 13.51) vs (83.17 ± 12.19) mmHg], uric acid [(411.79 ± 101.54) vs (379.96 ± 102.18) μmol/L], hemoglobin [(152.86 ± 30.70) vs (143.49 ± 21.15) g/L], pulmonary artery trunk width [(21.76 ± 3.94) vs (20.98 ± 3.34) mm], and ventricular septal thickness [(9.90 ± 1.70) vs (9.47 ± 1.60) mm] in the positive group ( n = 126) were significantly higher than those in the negative group ( n = 462, P < 0.01 or < 0.05). In multivariate logistic regression analysis, increased systolic blood pressure [odds ratio ( OR) = 1.015, 95% confidence interval (95% CI): 1.005 - 1.026], uric acid ( OR = 1.003, 95% CI: 1.001 - 1.005), and pulmonary artery trunk width ( OR = 1.058, 95% CI: 1.001 - 1.118) were risk factors for proteinuria; Tibetans had a decreased risk of proteinuria compared with Han ( OR = 0.505, 95% CI: 0.317 - 0.805), but increased hemoglobin had an increased risk of proteinuria compared with normal hemoglobin ( OR = 1.890, 95% CI: 1.231 - 2.903). Conclusion:In patients with hypertension at high altitude, increased hemoglobin, systolic blood pressure, uric acid, pulmonary artery trunk width, and Han nationality are risk factors for proteinuria.

Objective:To investigate the ultrasonographic features of internal jugular venous vein pseudo-aneurysm.Methods:The ultrasonographic and clinical features of a patient with internal jugular venous vein pseudo-aneurysm in Union Hospital Affiliated to Huazhong University of Science and Technology were retrospectively analyzed. These characteristics of this patient combined with cases from literatures were summarized.Results:Ultrasound showed that the 38.6 mm×14.0 mm×29.9 mm anechoic area in the soft tissue layer of the left neck communicated with the left internal jugular vein through the 3.8 mm wide breach, and a 12.9 mm×6.6 mm slightly hyperechoic mass was found in the anechoic area. Color Doppler flow imaging showed that the internal jugular vein communicated with the anechoic area through the crevasse. There was no obvious blood flow signal in slightly hyperechoic mass. The bidirectional burr-like blood flow signal could be detected by pulse-wave Doppler. Contrast enhanced ultrasound showed that the contrast agent flowed into the mass from the internal jugular vein through the breach, and the slightly hyperechoic mass appeared the contrast filling defect, and contrast agent was well filled in the rest of the anechoic area. Ultrasound diagnosis: left internal jugular vein pseudoaneurysm with thrombosis. 35 cases of cervical vein pseudo-aneurysm patients were finally included in 23 documents, including 12 males, 23 females, 15 cases on the left side, 20 cases on the right side, 6 cases of the internal jugular vein, 27 cases of the external jugular vein; one case only describes the neck veins and supraclavicular vein in another one case. Among them, 34 cases showed subcutaneous anechoic masses on ultrasound, 1 case showed slightly hyperechoic masses, and 35 cases showed venous wall breaches.Conclusions:Ultrasound examination has high diagnostic value for vein pseudo-aneurysm owing to its convenience, fast and serial observation. Therefore, it is the preferred method and can be widely used in clinical practice. Contrast-enhanced ultrasound can clearly show the blood perfusion, and help to improve the diagnostic confidence of the operator.

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.
Anesthesia ; Betacoronavirus ; isolation & purification ; Cesarean Section ; methods ; Coronavirus Infections ; complications ; Female ; Humans ; Infant ; Injections, Spinal ; Pandemics ; Pneumonia, Viral ; complications ; Pregnancy

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.
Anesthesia ; Betacoronavirus ; Cesarean Section ; Coronavirus Infections ; complications ; surgery ; Female ; Humans ; Infant ; Injections, Spinal ; Pneumonia, Viral ; complications ; diagnosis ; surgery ; Pregnancy ; Pregnancy Complications, Infectious ; surgery ; Pregnancy Outcome ; Preoperative Care

Objective To observe the effects of recombinant human B-type natriuretic peptide (rhBNP) on cardiac function and heart rate variability (HRV) in patients with heart failure after acute myocardial infarction (AMI). Methods One hundred and twenty patients with heart failure after AMI admitted to the Department of Cardiology of Cangzhou Central Hospital of Hebei Province from January 2015 to January 2018 were enrolled. The patients were divided into a conventional treatment group and an rhBNP treatment group according to random number table method, with 60 cases in each group. The two groups were treated according to the AMI guidelines, the conventional treatment group received west medicine anti-myocardial ischemia and anti-heart failure treatment; the rhBNP treatment group received rhBNP on the basis of routine treatment; the first load dose was 2 μg/kg intravenous injection impact treatment, followed by maintaining dose 8.5 ng·kg-1·min-1 intravenous drip for 7 days. The changes of hypersensitivity C-reactive protein (hs-CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) and HRV index were observed before and after treatment in the two groups [HRV indexes including the changes of average normal RR interval standard deviation (SDNN), the average value of the normal RR interval standard deviation (SDANN), the root mean square (RMSSD) of the adjacent RR interval difference, and the percentage of adjacent RR interval difference > 50 ms (PNN50)]; the incidences of adverse reactions in the two groups were observed. Results After treatment, the levels of hs-CRP and NT-proBNP in the two groups were significantly lower than those before treatment (all P < 0.05). LVEF, SDNN, SDANN, RMSSD and PNN50 were higher than those before treatment, and the changes of the above indicators in the rhBNP treatment group were more significant than those in the conventional treatment group [hs-CRP (mg/L): 6.2±3.3 vs. 11.8±5.5, NT-proBNP (ng/L): 2.5±2.0 vs. 6.4±4.3, LVEF: 0.49±0.02 vs. 0.44±0.04, SDNN (ms): 93.3±18.1 vs. 79.1±16.0, SDANN (ms): 87.3±17.8 vs. 70.9±14.9, RMSSD: 30.3±11.0 vs. 23.8±10.4, PNN50: (15.9±7.3)% vs. (9.6±5.5)%, all P < 0.05]; No significant adverse reactions occurred during the treatment of the two groups. Conclusion rhBNP can significantly improve the heart function of patients with heart failure after AMI, reduce the levels of inflammatory response indicators and improve HRV;since its clinical efficacy is good, and its application safe, it is worthy to promote its clinical use.

Objective To observe the effect of low-dose dabigatran etexilate on the clinical efficacy of elderly patients with venous thromboembolism (VTE). Methods Seventy-five elderly (≥ 80 years old) VTE patients admitted to Cangzhou Central Hospital from October 2016 to June 2018 were enrolled, they were treated according to the VTE guidelines, and low dose dabigatran etexilate was the anticoagulant therapy selected, 110 mg once daily for 6 months. After treatment for 6 months, the thrombus regression situation with color Doppler ultrasonography;clinical efficacy was evaluated by clinical symptoms and ultrasonographic results, the changes in platelet count (PLT), coagulation parameters [international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib)] before and after treatment were detected and the occurrence of adverse reactions were recorded and safety of drug was evaluated. Results There were no significant differences in PLT, INR and Fib before and after treatment [PLT (×109/L): 197.88±58.00 vs. 199.88±65.15, INR: 1.02±0.10 vs. 1.05±0.13, Fib (g/L): 2.89±0.67 vs. 2.84±0.70, all P > 0.05], the APTT after treatment was significantly prolonged compared with that before treatment (seconds:40.9±7.34 vs. 26.2±3.16), the difference being statistically significant (P < 0.05), the amount of APTT prolongation after treatment did not exceed 2 times [average (1.75±0.24) times] of the baseline value before treatment. The total effective rate of low-dose dabigatran etexilate for treatment of elderly patients with VTE for 6 months was 90.7% (68/75);no obvious adverse reactions occurred during the treatment. Conclusion Low-dose dabigatran etexilate for treatment of elderly patients with VTE is safe and effective without any obvious adverse reactions, and is worthy to be promoted for clinical use.