BACKGROUND:Osteonecrosis of the femoral head is a common orthopedic disease,and hip preservation surgery with bone grafting is commonly used in the early stage,in which autologous bone and allograft bone are commonly used as bone grafting materials.However,autologous bone transplantation is highly traumatic and bone supply is limited,and allograft bone is rich in sources,but there are serious risks of immune rejection and absorption.In recent years,the tissue engineering technique based on mesenchymal stem cells is a new method for the treatment of femoral head necrosis,which is gradually widely used after basic experiments and clinical application. OBJECTIVE:To review the application and prospect of tissue engineering in the treatment of osteonecrosis of the femoral head to provide a new choice for the clinical treatment of osteonecrosis of the femoral head. METHODS:The PubMed database and CNKI database from 2013 to 2023 were searched by the first author with Chinese and English search terms"tissue engineering,mesenchymal stem cells,biological scaffolds,cytokines,osteonecrosis of the femoral head,bone graft,hip preservation".The articles on the treatment of osteonecrosis of the femoral head with tissue engineering technology were selected,and 55 representative articles were included for review after the initial screening of all articles according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)With the continuous development of biotechnology and materials science,great progress has been made in the treatment of osteonecrosis of the femoral head by bone tissue engineering,such as the application of gene-modified mesenchymal stem cells to repair osteonecrosis,the combination of gene recombination technology and surface modification technology with bone tissue engineering in the treatment of osteonecrosis of the femoral head.(2)When applied to the necrotic femoral head,tissue engineering technology can promote the regeneration of necrotic bone tissue and the repair of the vascular system,provide biomechanical stability for the necrotic area,and use bioactive factors to accelerate the repair of seed cells to complete the regeneration of new bone in necrotic area.(3)However,most of these studies are still in the animal experiment stage,and there are still many unsolved problems and challenges in bone tissue engineering research.With the rapid development of nanotechnology,tissue engineering and clinical medicine,biomimetic replacement bone grafting materials with perfect performance are expected to come into being.(4)In the future,bone tissue engineering for osteonecrosis of the femoral head is expected to be a satisfactory treatment for patients with hip preservation.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c.1016delT (p.L339Rfs*5) and c.1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. CONCLUSION The child was diagnosed with 3-methylglutenedioic aciduria type VII. Discovery of the c.1016delT and c.1087A>G variants has enriched the mutational spectrum of the CLPB gene.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Base Sequence ; Metabolism, Inborn Errors/diagnosis* ; Mutation ; Neutropenia/genetics* ; Sequence Analysis, DNA

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

ObjectiveTo study the mechanism of Shenling Guchang prescription on blood glucose of gestational diabetes mellitus rats by regulating intestinal flora and short chain fatty acids. MethodThe 30 pregnant rats were randomly selected from 36 pregnant rats which were successfully pregnant. The model rats were fed with high-fat and high-sugar diet for 1 week， and 35 mg·kg^-1 streptozotocin （ STZ ） was given for 3 consecutive days to construct a gestational diabetes model. After successful modeling， the rats were randomly divided into model group， metformin group， Shenling Guchang prescription low-， medium- and high-dose group. The high dose group of Shenling Guchang prescription was given 18 mg·kg^-1， the middle dose group was given 9 mg·kg^-1， the low dose group was given 4.5 mg·kg^-1 drug solution by gavage， the metformin group was given 52.5 mg·kg^-1 drug solution by gavage， the blank group and the model group were given equal volume of normal saline by gavage.At 24 h after the last administration， blood samples were collected from the tail tip of the rats to measure the blood glucose， and blood samples were collected from the abdominal aorta under anesthesia to measure the levels of triglyceride （TG）， total cholesterol （TC）， high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C）. Lipopolysaccharides （LPS）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and insulin （INS） were detected by enzyme-linked immunosorbent assay （ELISA）.The intestinal tissue of rats was taken， and the pathological changes of intestinal tissue were observed by hematoxylin-eosin （HE） staining. Fecal samples were collected from rats， 16S rRNA sequencing was used to detect intestinal flora， and short-chain fatty acids were detected by gas chromatography. ResultCompared with the blank group， the incidence of adverse pregnancy outcomes in the model group was significantly increased （P<0.05）. Compared with the model group， the incidence of adverse pregnancy outcomes in the Shenling Guchang prescription groups and the metformin group was significantly decreased （P<0.05）. Compared with the blank group， the levels of blood glucose， TG， TC， HDL-C， LDL-C， LPS， IL-1β， IL-6 and TNF-α in the model group were significantly increased （P<0.05）， and the intestinal tissues had different degrees of inflammatory changes and mucosal damage. Compared with the model group， the levels of blood glucose， TG， TC， HDL-C， LDL-C， LPS， IL-1β， IL-6 and TNF-α in each group of Shenling Guchang prescription and metformin group were down-regulated （P<0.05）， and intestinal inflammation and intestinal mucosal damage were improved. Compared with the blank group， the functional structure and diversity of intestinal flora in the model group changed （P<0.05）. Compared with the model group， the functional structure and diversity of intestinal flora in the Shenling Guchang prescription groups and the metformin group were reversed， and the trend was close to the blank group （P<0.05）.Compared with the blank group， the abundance of pathogenic bacteria such as Escherichia coli， Enterococcus， Klebsiella， and Dustella in the model group was significantly increased， and the abundance of probiotics such as Prevotella， Prevotella， Akmania， Rombustella， and Lachnospiraceae was decreased （P<0.05）. Compared with the model group， the abundance of pathogenic bacteria such as Escherichia coli， Enterococcus， Klebsiella， and Dustella was decreased （P<0.05）， and the abundance of probiotic bacteria such as Prevotella， Akmanella， Rombustella， and Lachnospira was increased （P<0.05） in the Shenling Guchang prescription groups and the metformin group. Compared with the blank group， the content of short-chain fatty acids in the model group was significantly decreased （P<0.05）. Compared with the model group， the content of short-chain fatty acids in each group of Shenling Guchang prescription and metformin group increased （P<0.05）. Correlation analysis showed that Proteobacteria was positively correlated with inflammatory factors， blood glucose and blood lipid in gestational diabetes mellitus （P<0.05）. ConclusionShenling Guchang prescription has a good regulatory effect on blood glucose， blood lipids and adverse pregnancy outcomes in rats with gestational diabetes mellitus. Its efficacy is comparable to that of metformin sustained-release tablets. Its mechanism may be related to regulating the structure of intestinal flora， increasing the content of short-chain fatty acids， reducing LPS， IL-1β， IL-6， TNF-α， and improving intestinal inflammation.

Objective:To explore the effect of remote pulmonary rehabilitation management in chronic obstructive pulmonary disease (COPD) patients.Methods:From May 2017 to May 2019, convenience sampling was used to select 114 COPD outpatients in the Respiratory Department of the First Affiliated Hospital of Zhengzhou University. All patients were randomly divided into control group ( n=57) using conventional pulmonary rehabilitation management and observation group ( n=57) using remote pulmonary rehabilitation management, respectively, and the management period was one year. We compared the differences in COPD self-management ability, body mass index, airflow obstruction, dyspnea, exercise capacity (BODE) index, and average annual hospital admission rate between the two groups. Results:After intervention, the scores and the total score of self-management of observation group were higher than those of control group, and the differences were statistically significant ( P<0.01) . The dimension scores and the total score of self-management of observation group after the intervention were higher than those before intervention, and the differences were statistically significant ( P<0.05) . After intervention, the observation group's percentage of forced vital capacity in the first second to predicted value and the 6 minutes walking distance were higher than those of control group, and the dyspnea score and BODE index were lower than those of control group, and the differences were statistically significant ( P<0.05) . The average annual admission rate of the observation group and the control group were 5.41% and 9.06%, respectively. The average annual hospital admission rate of observation group was lower than that of control group, and the difference was statistically significant (χ 2=6.806, P=0.009) . Conclusions:Remote pulmonary rehabilitation management can improve the self-management ability of COPD patients, improve pulmonary function and reduce the admission rate of patients, which is worthy of clinical promotion.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

Objective To investigate the effects of Nod-like receptor protein 3 inhibitor MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE).Methods Ninety adult male C57BL/6 mice were randomly (random number) divided into three groups:the sham + saline group (n=20,sham group),CLP + saline group (n=35,CLP group),and CLP + MCC950 group (n=35,MCC950 group).SAE mouse model was established by cecal ligation and puncture (CLP) surgery.Saline (10 mL/kg) or MCC950 (10 mg/kg) was intraperitoneally injected 30 min before surgery and on day 1,2,4 and 6 after surgery according the grouping.Seven days after surgery,six mice were taken from each group.Western blot was used to detect the hippocampal content of NLRP3,apoptosis-associated specklike protein (ASC),interleukin-1β (IL-1β) and IL-18.The number of NLRP3-positive cells in CA 1 region were detected by immunohistochemical analysis.The remaining mice in each group were used for open field and fear conditioning tests 14 days after surgery.One-way analysis of variance was used for inter-group comparison,and SNK-q test was used for pairwise comparison.A P value ＜0.05 was considered statistically significant.Results Compared the MCC950 group with the CLP group,the freezing time of context test was significantly increased [(137±21) s vs (84±15) s,P=0.013],the hippocampal content of NLRP3,IL-1β and IL-18 were significantly reduced (P＜0.01),and the number of NLRP3-immunoreactive cells per mm2 in CA region were significantly decreased (23±5 vs 74±13,P＜0.01).There was no significant changes in protein level of ASC and results of open field tests (P＞0.05).Conclusions MCC950 administration can improve cognitive function in a mouse model of SAE,which is probably due to the inhibition of NLRP3 inflammasome and downstream inflammatory cytokines IL-1β and IL-18.