Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Hypertension is a common chronic disease with elevated arterial pressure as the main clinical manifestation，which can cause lesions in important organs such as heart，brain and kidney. In recent years，the prevalence of hypertension has increased，and its incidence is also increasing year by year. Combining the theory of traditional Chinese medicine （TCM） with personal clinical experience，Academician TONG Xiaolin put forward the specific pathogenesis of "disease-stage-state" of hypertension based on the state-target theory. Lipophagy plays an important role in the pathogenesis of hypertension by interfering with lipid metabolism，atherosclerosis，arterial plaque formation，vascular remodeling，vascular endothelial injury and other aspects of hypertension. Through modern medical and biological research，on the one hand，it is believed that the dynamic pathological changes in lipophagy are closely related to the "stage" of hypertensive state-target differentiation and treatment，corresponding to the time points of disease occurrence and development in the three stages of hypertension. On the other hand，it is believed that lipophagy is an important microscopic manifestation of the "state" of hypertensive state-target differentiation and treatment. From the perspective of lipophagy，this paper discusses the biological connotation of the 'disease-stage-state' model of state-target differentiation and treatment of hypertension and draws on the modern medicine to understand the law of disease development，matching the macro differentiation and treatment of TCM and the micro physico-chemical indicators of modern medicine to achieve precise TCM treatment. This study provides new ideas for the early prevention and treatment of hypertension and its complications.

Hepatic encephalopathy is a clinical syndrome of central nervous system dysfunction caused by liver insufficiency.It severely affects the quality of life of patients and may lead to death.Accurate prediction of the risk of developing hepatic encephalopathy is crucial for early intervention and treatment.In order to identify the risk of hepatic encephalopathy in patients in advance,many studies have been devoted to efforts to develop tools and methods to identify the risk of hepatic encephalopathy as early as possible,so as to develop preventive and early management strategies.Most conventional hepatic encephalopathy risk prediction models currently assess the prob-ability of a patient developing hepatic encephalopathy by analysing factors such as clinical data and biochemical indicators,however,their accuracy,sensitivity and positive predictive value are not high.The application of artificial intelligence to clinical predictive modelling is a very hot and promising area,which can use large amounts of data and complex algorithms to improve the accuracy and efficiency of diagnosis and prognosis.To date,there have been few studies using AI techniques to predict hepatic encephalopathy.Therefore,this paper reviews the research progress of hepatic encephalopathy risk prediction models,and also discusses the prospect of AI application in hepatic encephalopathy risk prediction models.It also points out the challenges and future research directions of AI in HE risk prediction model research in order to promote the development and clinical application of hepatic encephalopathy risk prediction models.

Objective:Explore the feasibility and advantages of using proximal and distal ends of thoracodosal artery and vein as recipient vessels in deep inferior epigastric perforator flap immediate breast reconstruction.Methods:The clinical data of patients who underwent breast reconstruction surgery using the proximal and distal ends of the thoracodorsal vein as recipient vessels at the Department of Breast and Thyroid Surgery of the Second Affiliated Hospital of Hainan Medical University from March 2022 to June 2023 were analyzed retrospectively. Preoperative examinations included thoracoabdominal angiography and color Doppler ultrasonic localization of the main trunk and perforators of the inferior epigastric vessels. The procedure began with mastectomy and axillary lymph node dissection, followed by the isolation of bilateral perforators and the main trunk of the abdominal flap. The main trunks of the bilateral inferior epigastric arteries were then transected, and their vascular pedicles exposed and anastomosed respectively to the proximal and distal ends of the thoracodorsal artery and vein. Both arteries and veins were joined end-to-end. The flap after trimming and reconstruction was then implanted into the cavity left after mastectomy through the incision. Breast positioning was performed with the patient in a knee-bent and hip-flexed position. After adjusting the shape of the reconstructed breast. The donor site was closed, the umbilicus was reconstructed, drainage tubes were placed, and the breast incision was closed. Postoperative follow-up monitored complications associated with the flap and patient satisfaction with the breast reconstruction, utilizing a self-assessment method.Results:Four female patients were included, aged (46.0±6.5) years, ranging from 37 to 52 years. All four patients had bilateral vascular pedicles in the donor area, with three patients having thoracodorsal vessels at the distal and proximal ends as recipient vessels, and one patient having anterior serratus branch of the thoracodorsal vessels at the distal and proximal ends. All drainage tubes were removed within 7 to 10 days after surgery. Patients were discharged. Follow-up period ranged from 1 to 15 months, averaging 6 months. The patients recovered well postoperatively, with no flap-related complications occurring. All four patients were satisfied with the result of the reconstruction.Conclusion:The simultaneous application of the proximal and distal ends of the thoracodorsal artery and vein can ensure the safety of flap survival while reducing damage to the ribs and intercostal muscles, achieving better aesthetic result.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To evaluate the long-term safety of related kidney donors after unilateral nephrectomy.Methods A total of 91 related donors who received nephrectomy in our hospital from 2006 to 2011 were followed up for at least 10 years by outpatient,telephone,or WeChat.During the follow-up period,the serum creatinine,serum uric acid,blood urea nitrogen,estimated glomerular filtration rate(eGFR),hematuria,urinary protein,blood pressure,blood glucose and blood lipids of the donors were detected,and the changes before and after nephrectomy were analyzed.Results At 1 month after operation,the levels of serum creatinine,blood urea nitrogen and serum uric acid of the donor were significantly higher than those before operation(all P＜0.05),but still within the normal range.The patients were followed up for 1,3,5 and 10 years after operation.Compared with 1 month after operation,the serum creatinine,blood urea nitrogen and serum uric acid were relatively stable(all P＞0.05).The eGFR of donors of different ages remained relatively stable for a long time after operation.There were 3 cases of endoscopic hematuria and 4 cases of proteinuria after surgery,and these symptoms were relieved after rest and symptomatic treatment.Ten(11.0%)donors developed hypertension 5(5.5%)developed hyperlipidemia,and 5(5.5%)developed diabetes mellitus.No patient died.Conclusion Nephrectomy is safe and feasible for healthy related donors.To ensure the safety of the donors,comprehensive evaluation before nephrectomy and regular follow-up after nephrectomy are essential.

Objective:Explore the feasibility and advantages of using proximal and distal ends of thoracodosal artery and vein as recipient vessels in deep inferior epigastric perforator flap immediate breast reconstruction.Methods:The clinical data of patients who underwent breast reconstruction surgery using the proximal and distal ends of the thoracodorsal vein as recipient vessels at the Department of Breast and Thyroid Surgery of the Second Affiliated Hospital of Hainan Medical University from March 2022 to June 2023 were analyzed retrospectively. Preoperative examinations included thoracoabdominal angiography and color Doppler ultrasonic localization of the main trunk and perforators of the inferior epigastric vessels. The procedure began with mastectomy and axillary lymph node dissection, followed by the isolation of bilateral perforators and the main trunk of the abdominal flap. The main trunks of the bilateral inferior epigastric arteries were then transected, and their vascular pedicles exposed and anastomosed respectively to the proximal and distal ends of the thoracodorsal artery and vein. Both arteries and veins were joined end-to-end. The flap after trimming and reconstruction was then implanted into the cavity left after mastectomy through the incision. Breast positioning was performed with the patient in a knee-bent and hip-flexed position. After adjusting the shape of the reconstructed breast. The donor site was closed, the umbilicus was reconstructed, drainage tubes were placed, and the breast incision was closed. Postoperative follow-up monitored complications associated with the flap and patient satisfaction with the breast reconstruction, utilizing a self-assessment method.Results:Four female patients were included, aged (46.0±6.5) years, ranging from 37 to 52 years. All four patients had bilateral vascular pedicles in the donor area, with three patients having thoracodorsal vessels at the distal and proximal ends as recipient vessels, and one patient having anterior serratus branch of the thoracodorsal vessels at the distal and proximal ends. All drainage tubes were removed within 7 to 10 days after surgery. Patients were discharged. Follow-up period ranged from 1 to 15 months, averaging 6 months. The patients recovered well postoperatively, with no flap-related complications occurring. All four patients were satisfied with the result of the reconstruction.Conclusion:The simultaneous application of the proximal and distal ends of the thoracodorsal artery and vein can ensure the safety of flap survival while reducing damage to the ribs and intercostal muscles, achieving better aesthetic result.

Objective:To explore the clinical characteristics and risk factors of pediatric kidney transplantation (KT).Methods:From January 1, 2010 to September 30, 2022, retrospective analysis was performed for the relevant clinical data of 81 pediatric recipients of primary KT at Organ Transplant Center of Shanghai Changzheng Hospital. The occurrences of acute rejection (AR) ,delayed graft function (DGF), infection, myelosuppression, tumor and other complications were observed within 1 year post-KT. They were grouped according to whether or not AR/DGF occurred. Univariate analysis speculated the effect of AR and DGF on renal function at 1 year after transplantation. Binary Logistic regression was employed for examining the risk factors related to AR/DGF.Results:During follow-ups, transplanted kidney was removed due to an embolization of renal vessels and dialysis resumed (n= 5). One child had failed graft due to the recurrence of original disease and dialysis resumed. The remaining 75 children had an excellent recovery of graft function. At the end of follow-ups, survival for transplant recipients and transplanted kidneys was 100% (81/81 ) and 92.6% (75/81) respectively. 23 patients (28.4%) developed DGF, including 20 child recipients of C-I donors. Among DGF recipients, 21 (91.3%) were immune induced with anti-CD25 humanized monoclonal antibody and 2 (8.7 %) with porcine antihuman lymphocyte immunoglobulin (pALG). Within the first year post-KT, 13 patients (16.1%) developed AR, including 11 child recipients of C-I donors. Induction was made with anti-CD25 humanized monoclonal antibody (n=8), pALG (n=4) and anti-human T lymphocyte rabbit immunoglobulin (n=1). And 12 cases were reversed with MP (methylprednisolone) shock therapy while another ineffective case was rescued by an intravenous infusion of rATG (rabbit anti-human thymocyte immunoglobulin). During postoperative follow-ups, 14 (17.3 %) KT recipients had an onset of pulmonary infection (n=7), upper respiratory tract infection (n=3), urinary tract infection (n=5), gastrointestinal infection (n=2) and abdominal cavity infection (n=1). The causative pathogens were bacteria (n=14) and viruses (n=4). Among 7 cases (8.6%) of myelosuppression, there were leukopenia (n=6) and thrombocytopenia (n=1 ). During 1-year follow-ups, no malignancy occurred. At the last follow-up, blood creatinine was (72.79±21.07) μmol/L in non-AR/DGF recipients. For AR/DGF recipients, blood creatinine levels were (68.83±10.78) and (74.20±18.70) μmol/L. There was no significant inter-group difference ( F=0.14, P=0.87). In groups with and without DGF, the incidence of bone marrow suppression in the children with DGF was significantly higher (21. 74 %) than that in the untreated group (3.45%), with a statistically significant difference ( P=0.02). However, there was no statistically significant difference in the age, sex, donor source, infection, and types of immune-induced drugs in AR, DGF occurrence and no occurrence group. logistic Regression analysis showed that immunoinduction therapy with lymphocyte inhibitor ( OR=0.074, 95 %CI: 0.009-0.0643, P=0.018) and bone marrow suppression ( OR=0.045, 95%CI: 0.004-0.515, P=0.013) were risk factors for DGF. Conclusion:KT in children may obtain decent outcomes. Immunoinduction therapy with lymphocyte inhibitors and occurrence of myelosuppression are risk factors for postoperative DGF. The occurrence of AR/DGF in early postoperative period does not affect the level of kidney function in children at 1 year post-KT. It is recommended to closely follow up and accumulate experiences for optimizing long-term outcomes.

OBJECTIVE: To explore the molecular reasons of weak expression of B antigen on the red cell. METHODS: Serological test for blood group was carried out, including red cell and plasma grouping, and anti-A1 and anti-H testing, and confirming weak A or B antigens by adsorption and elution. Exons 1-7 were sequenced directly, and one of them was cloned and sequenced. RESULTS: All of the 23 samples showed the weak B antigen by serological method. The alleles of the subgroups were identified by DNA sequencing, including 2 Bel subgroup, 4 B3 subgroup, 14 Bw subgroup, 2 CisAB subgroup and a novel allele. The novel allele showed a nucleotide substitution 662G>A in the exon 7, and the sequence was submitted to Blood Group Antigen Gene Mutation Database, and the novel allele was named Bel10. CONCLUSION Nucleotide substitution in exon results in blood subgroup, which showed that the antigens were weakened, and Bw phenotype was the most frequently subgroup.
ABO Blood-Group System/genetics* ; Alleles ; Exons ; Genotype ; Humans ; Nucleotides ; Phenotype