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.

[Objective] The purpose of this paper is to explore and summarize the experience of Professor ZHOU Xiaohong's treatment of non-erosive reflux disease(NERD),and promote the application in clinic.[Method] By following the professor ZHOU Xiaohong clinical copy and collecting related medical record,the autor summed up the viewpoints and medication experience of Professor ZHOU Xiaohong in the treatment of NERD,and referred to traditional Chinese medicine and western medicine literature as the theoretical basis,and attached to the corresponding test case,in order to verify.[Results] Professor ZHOU Xiaohong believes that the pathogenesis of NERD is closely related to the liver,and modern research has confirmed that it is affected by mental and psychological factors.Stagnated heat in liver and stomach is the basic pathogenesis,and to soothe the liver and relieve depression is basic treatment,and according to the severity of the disease stage,treatment is different.Clearing heat and normalizing the stomach at acute episode and relieving qi stagnancy in liver in relieving period.At the same time with relieving sore throat and resolving phlegm and eliminating stagnation medicine and symptomatic treatment,the qi regulating,and the disease can be cured.[Conclusion] Professor ZHOU Xiaohong has rich clinical experience and unique clinical effect,it is worth further study.

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

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.

Objective:To analyze the medication of one patient with ulcerative colitis to provide pharmaceutical care and support for rational drug use in patients with ulcerative colitis. Methods:During the treatment of the patient with severe ulcerative colitis, clin-ical pharmacists analyzed the drugs used by the patient and provided pharmaceutical care for doctors and the patient according to the ex-amination and diagnosis of the patient. Results:The compliance, therapeutic effect and medication safety of the patient were all im-proved by giving clinical drug rationalization suggestions and targeted medication monitoring and education, which fully embodied the necessity of work of clinical pharmacists in the medication of patients. Conclusion:Through case analysis, clinical thinking of clinical pharmacists can be developed to promote rational drug use, avoid adverse drug reactions and achieve optimal effect of drug treatment.

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.

Objective To introduce a case of ethylmalonic encephalopathy which is an autosomal recessive metabolic disorder caused by mutations in the ETHE1 gene. Methods The clinical course and gene mutation in a case of ethylmalonic encephalopathy was retrospectively analysed. Results A previously healthy girl presented with intractable diarrhea from the age of 7 months. Since then, progressive psychomotor regression has been observed. When she was 23 months, her blood butyr-ylcarnitine was signiifcantly increased (4.48μmol/L vs. normal range 0.0~1.0μmol/L), and isovalerylcarnitine (0.70μmol/L vs. normal range 0.0~0.65μmol/L) was also elevated. Her urine levels of ethylmalonic acid and methylsuccinate acid were markedly increased. Cranial MRI revealed bilateral basal ganglia lesions supporting the diagnosis of ethylmalonic encephalopathy. On her ETHE1 gene, a reported mutation (c.488G>A, p.R163Q) and a novel mutation (c.203T>C, p.L68P) were identiifed. After lactose-free dietary treatment and the supplements of L-carnitine, coenzyme Q10, vitamins B1, B2 and C, gradual improvement in general condition, intelligence and motor development has been observed. Conclusions Ethylmalonic aciduria is common in the patients with inborn errors of mitochondrial fatty acid beta-oxidation. In ethylmalonic encephalopathy, elevated blood levels of butyrylcarnitine and isovalerylcarnitine are common and ETHE1 sequencing is helpful in its diagnosis.