Objective To discuss the clinical efficacy of catheter-directed thrombolysis(CDT)in treating acute pulmonary embolism(APE).Methods A total of 215 patients with APE,who were admitted to the Second Affiliated Hospital of Shandong First Medical University of China,were enrolled in this study.Pulmonary angiography was performed in all the patients.After the location of the thrombus was identified,the pigtail catheter was rotated so as to break the thrombus into small pieces,which was followed by local infusion of thrombolytic agent urokinase to make recanalization of the occluded pulmonary artery.The postoperative clinical symptoms,blood oxygen saturation,mean pulmonary artery pressure,BNP,D-dimer,RV/LV diameter ratio were compared with their preoperative values.PESI scoring was used to evaluate the severity of the pulmonary embolism.Patients with PESI grade-Ⅲ and PESI grade-Ⅳ were classified into medium-risk group,and patients with PESI grade-V were classified into higher-risk group.Results Symptom relief immediately after surgery was observed in 210 patients,complete recanalization of pulmonary artery was achieved in 200 patients,and partial recanalization of pulmonary artery was seen in 15 patients.The preoperative mean pulmonary artery pressure,blood oxygen saturation,BNP,D-dimer,RV/LV diameter ratio were(46.24±5.32)mmHg,(90.36±3.23)％,(8 000.12±750.56)pg/mL,(7.5±2.3)mg/L and(1.63±0.22)respectively;at one week after surgery the above indicators were(26.12±3.36)mmHg,(98.74±2.12)％,(240.35±33.52)pg/mL,(1.75±0.36)mg/L and(1.11±0.13)respectively;the differences were statistically significant(all P＜0.05).In the patients who had symptoms of hemoptysis,shock and syncope before surgery,all these symptoms were completely disappeared in one week after CDT,and the symptoms of dyspnea,chest pain,and palpitations were significantly relieved after CDT,the differences were statistically significant(all P＜0.05).The difference in survival time between different PESI grade groups was statistically significant(P＜0.05).No serious postoperative complications such as severe arrhythmia,cerebral hemorrhage,or gastrointestinal bleeding occurred.Postoperative 3-month CT pulmonary angiography(CTPA)showed that the main pulmonary artery was well visualized and no thrombus-produced filling defect shadow was detected.Conclusion For the treatment of APE,CDT can promptly and rapidly open the obstructed pulmonary artery lumen,restore pulmonary artery hemodynamics,and correct hypoxemia.Therefore,CDT is a safe,effective and quick treatment for APE.

This paper summarized PENG Qinghua's clinical experience in treating dry eye by applying therapeutic method of maintaining with sweet medicinals and restoring the body fluids. It is believed that the spleen earth insufficiency and fluids damage transforming into dryness are the main pathogenesis of the disease， and the basic therapeutic principle is maintaining with the sweet and restoring the body fluids by mainly using sweet medicines. It is advocated to use mild-sweet herbs， such as Baibiandou （Lablab purpureus subsp. purpureus）， Fuling （Smilax glabra Roxb.）， and Yiyiren （Coix lacryma-jobi L.）， to transport spleen earth， so that qi is restored and body fluids are recovered； moderate-sweet herbs， such as Dangshen （Codonopsis pilosula ［Franch.］ Nannf.）， Taizishen （Pseudostellaria heterophylla ［Miq.］ Pax）， Shanyao （Dioscorea oppositifolia L.） and Zhigancao （Glycyrrhiza glabra L.） are suggested to cultivate earth and generate metal， so as to move qi and circulate fluid； sweet-cool herbs， such as Nanshashen （Adenophora triphylla ［Thunb.］ A.DC.）， Beishashen （Glehnia littoralis ［A.Gray］ F.Schmidt ex Miq.）， Yuzhu （Polygonatum odoratum ［Mill.］ Druce）， Tianhuafen （Trichosanthes kirilowii Maxim.） are suggested to nourish yin and increase body fluids， so as to promote fluid production to moisten dryness. In this way， when the source of fluid is restored and the fluid is circulated， the fluid can be produced continuously， which provides new ideas for the treatment of dry eyes with traditional Chinese medicine.

Objective:To investigate the efficacy and safety of hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors in treatment of gastric cancer with ascites.Methods:A retrospective case-control study was conducted. The clinical data of 39 gastric cancer patients with malignant ascites treated in Xi'an Third Hospital from May 2021 to June 2023 were retrospectively analyzed. All patients were divided into the routine group (18 cases) and the observation group (21 cases) according to different treatment methods. The patients in the routine group were treated with hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy; the patients in the observation group were treated with immune checkpoint inhibitors on the basis of hyperthermic intraperitoneal chemotherapy combined with systemic intravenous chemotherapy. The clinical efficacy, tumor marker levels, Karnofsky scores, and incidence of adverse reactions of both groups were compared. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups.Results:There were 12 males (66.7%) and 6 females (33.3%) in the routine group, with the age of (57±13) years; 13 males (61.9%) and 8 females (38.1%) in the observation group, with the age of (59±12) years. After treatment, the serum carcinoembryonic antigen (CEA), carbohydrate 125 (CA125), carbohydrate 199 (CA199) levels in the 2 groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). After treatment, the serum CEA, CA125, CA199 levels in the observation group were lower than those in the routine group, and the differences were statistically significant (all P < 0.05). After treatment, Karnofsky scores in the observation group were higher than those before treatment [(78.6±7.5) scores vs. (69.5±8.9) scores], and Karnofsky scores in the observation group were higher than those in the routine group [(78.6±7.5) scores vs. (72.8±7.9) scores],and the differences were statistically significant ( t = -3.65, 2.33, all P < 0.05). The objective remission rate (ORR) was 55.6% (10/18) and 71.4%(15/21), respectively in the routine group and the observation group, and the difference was statistically significant ( χ2 = 9.24, P = 0.002). The median OS time was 38.97 months (95% CI: 34.99-42.95 months) and 23.62 months (95% CI: 18.49-28.74 months), respectively in the observation group and the routine group, and the difference was statistically significant ( χ2 = 3.88, P = 0.049). There was no statistically significant difference in the incidence of adverse events between the 2 groups (all P > 0.05). No serious treatment-related complications were found in the observation group. Conclusions:Hyperthermic intraperitoneal chemotherapy combined with immune checkpoint inhibitors shows a good therapeutic effect in the treatment of gastric cancer with ascites, and the adverse reactions are controllable.

Objective: To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated. Methods: Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families. Results: Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis. Conclusion Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.

OBJECTIVEWe report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China.

METHODThe clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.

RESULTThe proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition.

CONCLUSIONA boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.

Amino Acid Metabolism, Inborn Errors ; complications ; Brain Diseases ; chemically induced ; Carnitine ; analogs & derivatives ; Diet, Protein-Restricted ; Hepatitis B Vaccines ; adverse effects ; Humans ; Infant ; Male ; Methylmalonic Acid ; urine ; Mutation ; Vaccination ; adverse effects ; Vitamin B Complex ; Vomiting

Objective To investigate the clinical,biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014,a total of 126 patients with isolated methyl-malonic aciduria from Peking University First Hospital were enrolled in this study. In 60 patients,gene analysis was per-formed. The clinical characteristics,laboratory findings,treatment and outcomes were retrospectively analyzed. Results Among the 126 patients,only 3 cases(2. 4% )were detected through newborn screening and treated with dietary in-tervention,cobalamin and L - camitine. The age at onset of 123 cases(97. 6% )varied from a few hours after birth to 7 years and 11 months old. The common presentations were recurrent vomiting,mental retardation,poor feeding,lethargy, respiratory distress,coma,seizures,cutaneous lesion and jaundice with 11 patients(8. 73% )dead. Abnormal family his-tory was found in 27(21. 4% )patients. Metabolic acidosis and anemia were frequent laboratory findings. Basal ganglia damage and white matter changes were observed in most patients. Sixty patients got genetic analysis,and 58 cases of them had MUT gene mutations. One case had MMAA defect. One case had MMAB defect. In MUT gene,12 novel muta-tions were identified. After treatment,mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex,and prone to appear metabolic crisis. MUT defect is the main cause. Early metabolic investigation is very im-portant to reach diagnosis. Newborn screening,early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap.

OBJECTIVEArgininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia.

METHODThree boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis.

RESULTSeven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn.

CONCLUSIONArgininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.

Abortion, Induced ; Amniocentesis ; Arginase ; Arginine ; blood ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; DNA Mutational Analysis ; Diet, Protein-Restricted ; Exons ; Female ; Fetus ; Genotype ; Homozygote ; Humans ; Hyperammonemia ; diagnosis ; Hyperargininemia ; diagnosis ; physiopathology ; Infant ; Infant, Newborn ; Male ; Mutation ; Phenotype ; Pregnancy ; Prenatal Diagnosis ; Quadriplegia ; diagnosis ; physiopathology ; Seizures

OBJECTIVETo investigate the clinical, biochemical and genetic profiles of 28 Chinese patients with glutaric aciduria type 1.

METHODTwenty-eight patients with glutaric aciduria type 1 seen in the Department of Pediatrics, Peking University First Hospital from July 2003 to October 2013 were studied. The data of clinical course, laboratory examinations, cranial MRI and GCDH gene mutations of the patients were analyzed.

RESULT(1) Three cases were detected by newborn screening, and the other patients were diagnosed at the age of 2 months to 17 years. (2) 22 patients (79%) were infant onset cases with psychomotor retardation, dystonia, seizures, athetosis, recurrent vomiting, drowsiness or feeding difficulty. Only two of the 22 patients with infant onset got normal intelligence and movement after treatment. Twenty of them were improved slowly with delayed development, dystonia and other neurological problems. Three patients (11%) had late onset. They had motor regression, headache and seizure at the age of 8, 9 and 17 years, respectively. Rapid improvement was observed after treatment. (3) Cranial MRI has been checked in 23 patients; 22 of them showed characteristic widening of the Sylvian fissure, abnormalities of the basal ganglia, leukoencephalopathy and brain atrophy. Thirty-five mutations in GCDH gene of the patients were identified; c.148T>C (p.W50R) was the most common mutation with the frequency of 7.7%; 6 mutations (c.628A>G, c.700C>T, c.731G>T, c.963G>C, c.1031C>T and c.1109T>C) were novel.

CONCLUSIONGlutaric aciduria type 1 usually induced neurological deterioration resulting in severe psychomotor retardation and dystonia. Most of our patients were clinically diagnosed. Patients with early onset usually remained having neurological damage. Phenotype and genotype correlation has not been found in the patients. Neonatal screening for organic acidurias should be expanded in China.

Age of Onset ; Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; metabolism ; Brain Diseases, Metabolic ; diagnosis ; genetics ; metabolism ; DNA Mutational Analysis ; Follow-Up Studies ; Gas Chromatography-Mass Spectrometry ; Glutarates ; urine ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; metabolism ; Humans ; Infant, Newborn ; Intellectual Disability ; etiology ; pathology ; Magnetic Resonance Imaging ; Movement Disorders ; etiology ; pathology ; Mutation ; Neonatal Screening ; methods ; Retrospective Studies

Objective To explore the clinical, therapeutic and genetic features of IVD gene in late-onset non-classical isovaleric aciduria. Methods One boy and two girls presented with intractable vomiting were admitted. Urine organic acids and blood acylcarnitines proifles were analyzed. Isovaleric aciduria was diagnosed and conifrmed by IVD gene analysis. The patients were treated with leucine-restricted diet and the supplements of L-carnitine and glycine. Results Three patients had recurrent vomiting, drowsiness, odor of sweaty feet and metabolic acidosis from the age of 1 to 2 years. All of them had normal intelligence and leukopenia. One had oligocythemia. The blood isovalerylcarnitines (4.6 to 8.2μmol/L) and urine isovalerylglycines (36.1 to 1783.56 mmol/mmol creatinine) were elevated. Six mutations were found in their IVD gene. Four mutations (c.157C>T, c.214G>A, c.1183C>G and c.1208A>G) were reported. Two (c.1039G>A and c.1076A>G) were novel. The patients completely recovered after treatment with protein-restricted diet and the supplements of L-carnitine and glycine. Currently, they were aged 19 months to 14 years with normal physical and psychomotor development. Conclusions The clinical features of late-onset non-classical isovaleric aciduria are complex. It is onset in infants and young children and characteristic of recurrent vomiting and metabolic acidosis, which can be diagnosed by the blood acylcarnitine spectrum, urine organic acid analysis, and conifrmed by genetic analysis. L-carnitine supplement and diet intervention has signiifcant effects.

Objectives To report the ifrst Chinese case of early onset argininosuccinic aciduria. Methods A girl aged three days was admitted because of vomiting and lethargy from the second day of life. General laboratory examination, blood amino acids analysis, urine organic acids tests and gene studies were performed for the diagnosis. Results Severe hyperam-monemia, liver dysfunction, metabolic acidosis, hypokalemia and hypocalcemia were found. Bood citrulline was extremely elevated (1098.12μmol/L vs normal range 5 to 25μmol/L), while blood arginine was decreased. Urine orotic acid, uracil and argininosuccinic acid were signiifcantly elevated. Two known heterozygosis mutations on ASL gene, c.544C>T (p.R182X) and c.706C>T (p.R236W), conifrmed the diagnosis of argininosuccinic aciduria. Unfortunately, protein-restricted diet with L-arginine supplement showed no effect. The patient died at the 23th day of life. Conclusions Argininosuccinic aciduria is a severe inherit-ed metabolic disorder. Clinical diagnosis is dififcult. It is characterized biochemically by severe citrullinemia. Urine organic acids analysis and ASL gene analysis are important for the differential diagnosis. In this study, a case of neonate death due to early-on-set argininosuccinic aciduria was diagnosed by post-mortem investigation. ASL gene study is helpful for the genetic counseling and prenatal diagnosis of the disease.