Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

Objective:To retrieve, evaluate, and integrate evidence on output and input record in patients with heart failure.Methods:Literature related to output and input record for patients with heart failure was systematically searched in national and international guideline networks, professional association websites, and databases. The search period was from database establishment to October 31, 2024. Evidence was extracted, integrated, and graded after two researchers independently conducted a literature quality assessment.Results:A total of 15 papers were included, including six guidelines, two expert consensus, two evidence summaries, one recommended practice, two systematic reviews, and two expert opinions. Twenty-five pieces of best evidence were summarized in five areas of objects and content, fluid measurement, recording and aggregation, evaluation and monitoring, and training and guidance.Conclusions:This study summarizes the best evidence for output and input record in patients with heart failure, which may inform nursing staff in their clinical practice. Nursing staff should judiciously select and apply evidence in a clinical context so as to improve the accuracy of output and input record.

Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Objective:To explore the application indications, clinical characteristics and influencing factors of extracorporeal membrane oxygenation (ECMO) in the treatment of critically ill pregnant and postpartum women in Bao′an district, Shenzhen, and summarize regional experience.Methods:A retrospective analysis was conducted on 5 cases of pregnant and postpartum women who received ECMO treatment at the CUHK Women′s and Children′s Medical Centre (Shenzhen) and the Shenzhen Bao′an People′s Hospital from 2020 to 2024. Baseline characteristics, ECMO parameters, complications and maternal-infant outcomes of the patients were collected.Results:The patients′ age was 29(24, 36) years old, gestational age was 39(31, 39) weeks, and ECMO maintenance time was 8(4, 8) days. ECMO indications included 2 cases of cardiac arrest, 1 case of respiratory and circulatory failure, 1 case of cardiogenic shock, and 1 case of acute respiratory distress syndrome. There were 4 cases of veno-arterial (VA)-ECMO and 1 case of veno-venous (VV)-ECMO. Complications included 3 cases of bleeding, 4 cases of acute renal failure, 2 cases of thrombosis, and 2 cases of infection. Both maternal and infant survival were 3 cases. Successful cases benefited from the multidisciplinary rapid response team and regional transportation cooperation, while failed cases were mostly accompanied by severe bleeding and disseminated intravascular coagulation.Conclusions:ECMO improves the success rate of treating critically ill pregnant and postpartum women in Bao′an District. Amniotic fluid embolism and severe pulmonary hypertension are the main indications. Regional multidisciplinary cooperation, accurate initiation timing and individualized anticoagulation management are the keys. It is recommended to establish a national ECMO registration system for pregnant and postpartum women to optimize treatment strategies and improve maternal and infant prognosis.

Objective:To retrieve, evaluate, and integrate evidence on output and input record in patients with heart failure.Methods:Literature related to output and input record for patients with heart failure was systematically searched in national and international guideline networks, professional association websites, and databases. The search period was from database establishment to October 31, 2024. Evidence was extracted, integrated, and graded after two researchers independently conducted a literature quality assessment.Results:A total of 15 papers were included, including six guidelines, two expert consensus, two evidence summaries, one recommended practice, two systematic reviews, and two expert opinions. Twenty-five pieces of best evidence were summarized in five areas of objects and content, fluid measurement, recording and aggregation, evaluation and monitoring, and training and guidance.Conclusions:This study summarizes the best evidence for output and input record in patients with heart failure, which may inform nursing staff in their clinical practice. Nursing staff should judiciously select and apply evidence in a clinical context so as to improve the accuracy of output and input record.

Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Objective:To explore the application indications, clinical characteristics and influencing factors of extracorporeal membrane oxygenation (ECMO) in the treatment of critically ill pregnant and postpartum women in Bao′an district, Shenzhen, and summarize regional experience.Methods:A retrospective analysis was conducted on 5 cases of pregnant and postpartum women who received ECMO treatment at the CUHK Women′s and Children′s Medical Centre (Shenzhen) and the Shenzhen Bao′an People′s Hospital from 2020 to 2024. Baseline characteristics, ECMO parameters, complications and maternal-infant outcomes of the patients were collected.Results:The patients′ age was 29(24, 36) years old, gestational age was 39(31, 39) weeks, and ECMO maintenance time was 8(4, 8) days. ECMO indications included 2 cases of cardiac arrest, 1 case of respiratory and circulatory failure, 1 case of cardiogenic shock, and 1 case of acute respiratory distress syndrome. There were 4 cases of veno-arterial (VA)-ECMO and 1 case of veno-venous (VV)-ECMO. Complications included 3 cases of bleeding, 4 cases of acute renal failure, 2 cases of thrombosis, and 2 cases of infection. Both maternal and infant survival were 3 cases. Successful cases benefited from the multidisciplinary rapid response team and regional transportation cooperation, while failed cases were mostly accompanied by severe bleeding and disseminated intravascular coagulation.Conclusions:ECMO improves the success rate of treating critically ill pregnant and postpartum women in Bao′an District. Amniotic fluid embolism and severe pulmonary hypertension are the main indications. Regional multidisciplinary cooperation, accurate initiation timing and individualized anticoagulation management are the keys. It is recommended to establish a national ECMO registration system for pregnant and postpartum women to optimize treatment strategies and improve maternal and infant prognosis.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.

A 1-year and 9-month-old male proband presented with clustered rice grain-sized flat smooth red papules on the face, trunk and limbs for 1.5 years, without fever, joint swelling, or pain. The proband′s sister aged 7 years ever experienced swelling and pain in the finger joints of both hands at the age of 2 years, and had intermittent fever and papules all over the body at the same time, and the papules gradually regressed with the subsidence of fever. The proband′s mother aged 27 years suffered from swelling and pain in the finger joints of both hands when she was young, gradually leading to finger deformities, and experienced intermittent knee swelling and pain at the age of 12 years without obvious skin lesions on the body. No abnormality was found in ophthalmological and systemic physical examinations of the 3 patients. Whole-exome sequencing showed that the proband, his sister and mother all had a heterozygous missense mutation c.1001G>A (p.R334Q) in exon 4 of the NOD2 gene. A diagnosis of Blau syndrome was made. The proband was treated with topical moisturizing cream all over the body; during the 52-week follow-up, no joint swelling and pain or eye symptoms were found in the proband, while erythema and depressed scars were observed on the face, trunk and limbs. The proband′s sister and mother were treated with subcutaneous injections of adalimumab at initial doses of 40 mg and 80 mg respectively, followed 1 week later by injections at 20 mg and 40 mg respectively, and then treated with injections at 20 mg and 40 mg respectively every 2 weeks; after 12-week treatment, the joint swelling and pain were markedly relieved in the proband′s sister and mother, and most skin lesions subsided in the proband′s sister; at week 52 during the follow-up, there was no joint swelling, pain or skin lesions in the proband′s sister, and there was no swelling or pain in the knee joints of the proband′s mother, while no improvement was observed in her finger deformities. During the treatment, no eye symptoms or adverse reactions were observed neither in the proband′s sister nor in his mother.

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.