OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To review the research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells (MSCs). METHODS: An extensive review of the relevant literature on bone repair biomaterials, particularly those designed to recruit endogenous MSCs, was conducted, encompassing both domestic and international studies from recent years. The construction methods and optimization strategies for these biomaterials were summarized. Additionally, future research directions and focal points concerning this material were proposed. RESULTS: With the advancement of tissue engineering technology, bone repair biomaterials have increasingly emerged as an ideal solution for addressing bone defects. MSCs serve as the most critical "seed cells" in bone tissue engineering. Historically, both MSCs and their derived exosomes have been utilized in bone repair biomaterials; however, challenges such as limited sources of MSCs and exosomes, low survival rates, and various other issues have persisted. To address these challenges, researchers are combining growth factors, bioactive peptides, specific aptamers, and other substances with biomaterials to develop constructs that facilitate stem cell recruitment. By optimizing mechanical properties, promoting vascular regeneration, and regulating the microenvironment, it is possible to create effective bone repair biomaterials that enhance stem cell recruitment. CONCLUSION In comparison to cytokines, phages, and metal ions, bioactive peptides and aptamers obtained through screening exhibit more specific and targeted recruitment functions. Future development directions for bone repair biomaterials will involve the modification of peptides and aptamers with targeted recruitment capabilities in biological materials, as well as the optimization of the mechanical properties of these materials to enhance vascular regeneration and adjust the microenvironment.
Mesenchymal Stem Cells/metabolism* ; Biocompatible Materials/chemistry* ; Tissue Engineering/methods* ; Humans ; Bone Regeneration ; Tissue Scaffolds/chemistry* ; Animals ; Bone and Bones ; Mesenchymal Stem Cell Transplantation/methods* ; Exosomes/metabolism* ; Intercellular Signaling Peptides and Proteins/metabolism* ; Osteogenesis

Objective:To investigate the relationship of the acute radiation reactions of totalbody irradiation before hematopoietic stem cell transplantation with the different total and fractionated doses of irradiation.Methods:The clinical data of 48 patients who underwent 6 MV X-ray total body irradiation pretreatment from May 2015 to December 2019 in Shijiazhuang Ping'an Hospital before undergoing hematopoietic stem cell transplantation were retrospectively analyzed. The patients were divided into 8 Gy group (12 cases), 10 Gy group (31 cases) and 12 Gy group (5 cases) according to the total radiation dose, and divided into 4 Gy/f group (17 cases) and 5 Gy/f group (31 cases) according to the fractionated radiation dose. Acute radiation reactions in the oral mucosa, pharynx, salivary glands, upper gastrointestinal tract, lower gastrointestinal tract and lung of patients in each group after radiotherapy were summarized and compared.Results:Acute pharyngeal reaction in the total radiation dose of 8 Gy group showed that 11 cases (91.7%) were grade 0 and 1 case (8.3%) was grade 1; in the total radiation dose of 10 Gy group, 10 cases (32.3%) were grade 0, 13 cases (41.9%) were grade 1, 4 cases (12.9%) were grade 2, 3 cases (9.7%) were grade 3, and 1 case (3.2%) was grade 4; in the total radiation dose of 12 Gy group, 2 cases (40.0%) were grade 0, 1 case (20.0%) was grade 1, 1 case (20.0%) was grade 2, and 1 case (20.0%) was grade 3. The severity of acute pharyngeal radiation reaction in the total radiation dose of 8 Gy group was better than that in the 10 Gy and 12 Gy groups, and the difference was statistically significant ( χ2 = 11.338, P = 0.003); there was no significant difference in the incidence of acute radiation reactions in other parts (all P > 0.05). Acute pharyngeal radiation reaction in the fractionated radiation dose of 4 Gy/f group showed that 13 cases (76.5%) were grade 0, 2 case (11.8%) was grade 1, 1 case (5.9%) was grade 2, and 1 case (5.9%) was grade 3; in the 5 Gy/f group, 10 cases (32.3%) were grade 0, 13 cases (41.9%) were grade 1, 4 cases (12.9%) were grade 2, 3 cases (9.7%) were grade 3, and 1 case (3.2%) was grade 4. The severity of acute pharyngeal radiation reaction in the fractionated radiation dose 4 Gy/f group was better than that in the 5 Gy/f group, and the difference was statistically significant ( Z = -2.606, P = 0.009); there was no significant difference in the incidence of acute radiation reactions in other parts (all P > 0.05). Conclusion:The total dose of 8 Gy and fractionated dose of 4 Gy/f in the total body irradiation before hematopoietic stem cell transplantation can alleviate the acute pharyngeal radiation reaction.

OBJECTIVE: To explore the clinical and genetic characteristics of five pedigrees affected with hereditary spastic paraplegia(HSP). METHODS: Clinical data of the five pedigrees was collected, and high-throughput sequencing was carried out to detect potential variants. Sanger sequencing were used to verify the results. RESULTS: The probands of pedigree 1 and 2 were found to harbor heterozygous SPAST gene variants, namely c.1196C>T and c.1523T>A. The proband of pedigree 3 harbored compound heterozygous variants of FA2H gene (c.61G>C and c.688G>A). Proband from pedigree 4 harbored compound heterozygous variants of SPG11 gene (c.6812+4_6812+7delAGTA and c.915delT). The proband of pedigree 5 harbored compound heterozygous variants of SPG7 gene (c.1703_1704delAG and c.1937-1G>C). Based on the American College of Medical Genetics and Genomics(ACMG) guidelines, all variants were predicted to be likely pathogenic. Among these, SPAST gene c.1523T>A, FA2H gene c.61.G>C, SPG11 gene splicing region c.6812+4_6812+7delAGTA, c.915delT, SPG7 gene c.1703_1704delAG and splicing region c.1937-1G>C variants were unreported previously. CONCLUSION The probands of pedigrees 1 and 2 were diagnosed with autosomal dominant hereditary spastic paraplegia type 4, for which pedigree 2 showed incompletely penetrance. Pedigrees 3, 4, and 5 were diagnosed with autosomal recessive hereditary spastic paraplegia type 35, 11 and 7, respectively. Above result provided a reference for clinical diagnosis and genetic counseling for the affected pedigrees.

OBJECTIVE: The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis. METHODS: The probands were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines. RESULTS: A homozygous variant in the CYP4V2 gene c. (802-8) _810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1, parents did not detect; CYP4V2 genes c. (802-8)_810delTCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers. The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing. The c. (802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant, and both splicing variant and nonsense variant could produce truncated nonfunctional protein products. Based on standards and guidelines by American College of Medical Genetics and Genomics, the CYP4V2 genes c. (802-8)_810del TCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) were predicted to be pathogenic variants (PVS1+PS1+PM2+PM3). CONCLUSION The homozygous variant c. (802-8) _810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c. (802-8) _810delTCATACAGGTCATCGCTinsGC and c.958C>T (p.Arg320X) in CYP4V2 gene are the cause of the disease in the probands of two pedigrees , respectively.
Corneal Dystrophies, Hereditary/pathology* ; Cytochrome P450 Family 4/genetics* ; Genetic Variation ; Humans ; Mutation ; Pedigree ; Phenotype ; Retinal Diseases/pathology*

OBJECTIVE： To establish a method for the concentration determination of levofloxacin in rat plasma and compare the pharmacokinetic difference between Levofloxacin tablets and gastric floating sustained-release pellets in rats. METHODS： SD rats were randomly divided into Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group， with 6 rats in each group. They were given relevant medicine intragastrically 40 mg/kg （taking normal saline as solvent）， and the blood samples 0.3 mL were collected before medication and 0.25， 0.5， 1， 2， 4， 8， 12， 24 h after medication. The plasma concentration of levofloxacin in rats was determined by UPLC. The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid-acetonitrile （78 ∶ 22，V/V） at the flow rate of 0.3 mL/min. The detection wavelength was set at 294 nm， and column temperature was 40 ℃. The sample size was 2 μL. The pharmacokinetic parameters of rats were calculated by using DAS 3.0 software， and the difference between them were detected by F-test. RESULTS： The linear range of levofloxacin was 0.20-20.12 μg/mL， and limit of quantitation was 0.20 μg/mL. The limit of detection was 0.04 μg/mL. The intra-day and inter-day RSDs were less than 10％. The recoveries were all in line with the related requirements of quantitation analysis of the biological samples stated in 2015 edition of Chinese Pharmacopeia. Average drug concentration-time curves of single dose of Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group were all in line with two-compartment model after intragastric administration. The pharmacokinetic parameters cmax were （12.13±1.67） and （8.76±1.13） μg/mL； tmax were（0.86±0.15） and （2.48±0.45）h； t1/2β were（4.67±0.95） and （6.67±1.01）h； AUC0-t were （42.95±4.21） and （126.48±9.44） μg·h/mL； AUC0-∞ were （50.66±6.72） and （132.61±10.63） μg·h/mL， respectively. Compared with Levofloxacin tablets， cmax of Levofloxacin gastric floating sustained-release pellets were decreased significantly， and tmax， t1/2β， AUC and mean retention time were prolonged or increased significantly （P＜0.05）， and relative bioavailability was 294％. CONCLUSIONS： Established UPLC method is simple， specific， sensitive and precise， and can be used for the determination of levofloxacin concentration in rat plasma and its pharmacokinetic study. After levofloxacin is made into gastric floating sustained-release pellets， pharmacokinetic parameters are changed significantly， retention time is prolonged significantly and bioavailability is improved significantly.

Objective To investigate the effect of section of pancreatic envelope combined with vacuum sealing drainage under laparoscopy on inflammatory mediators of patients with early severe acute pancreatitis (SAP). Methods Forty-two SAP patients were admitted to Foshan Hospital of Traditional Chinese Medicine in Guangdong Province from January 2008 to December 2016. That 22 patients underwent pancreatic membrane incision and vacuum sealing drainage under laparoscopy was in the experimental group, and that 20 patients underwent the routine pancreatic membrane incision and double tube drainage was in the control group. The venous blood was collected, the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured before and after operation for 1, 3, 7 and 14 days, and the clinical therapeutic effects were observed in the two groups. Results With the prolongation of therapy, the levels of CRP, IL-6 and TNF-α were decreased continuously in both groups, the degrees of decrease of above indexes in experimental group were more significant than those in the control group, and the differences in these indexes between the two groups were statistically significant [CRP (mg/L): 1 day was 203.80±25.12 vs. 271.79±60.41, 3 day was 117.26±19.70 vs. 174.53±42.37; IL-6 (ng/L): 1 day was 40.63±3.38 vs. 57.10±11.46, 3 days was 23.14±3.51 vs. 46.87±10.69; TNF-α (ng/L): 1 day was 23.91±10.42 vs. 36.73±15.90, 3 days was 19.13±8.34 vs. 32.58±15.81, all P < 0.05]. There were no statistical significant differences in the levels of above indexes on 7 days and 14 days after treatment between the two groups (all P > 0.05). The therapeutic efficacy of the experimental group was significantly higher than that of the control group [95.45% (21/22) vs. 90.0% (18/20), P < 0.05]. Conclusion Under laparoscopy, pancreatic envelope incision combined with vacuum sealing drainage performed for early SAP patients can control the body inflammation more rapidly, reduce complications and shorten the disease course.

Objective: To investigate the effect of receptor interacting protein kinase 4 (RIPK4) gene silencing on tumor necrosis factor-a (TNF-a)-induced apoptosis of human osteosarcoma MG-63 cells. Methods: The specific siRNA targeting RIPK4 gene (RIPK4-siRNA) was transfected into MG-63 cells by liposome (named as RIPK4-siRNA group), while the MG-63 cells were transfected with negative control-siRNA (NC-siRNA) as the negative control (named as NC-siRNA group). Then the MG-63 cells transfected with RIPK4-siRNA were treated with human recombinant TNF-a (named as RIPK4-siRNA+TNF-a group), while the MG-63 cells were only treated with TNF-a as the positive control (named as TNF-a group). The proliferation of MG-63 cells was detected by 5-ethynyl-2'-deoxyuridine (EdU) method. The apoptosis of MG-63 cells was detected by Hoechst 33258 staining. The expressions of RIPK4, Bax, Bcl-xL and caspase-3 proteins in MG-63 cells were examined by Western blotting. Results: The expression level of RIPK4 protein in MG-63 cells was significantly down-regulated after transfection of RIPK4-siRNA (P < 0.05). The EdU positive rates of RIPK4-siRNA, NC-siRNA, TNF-a and RIPK4-siRNA+TNF-a groups were 60.7%, 39.6%, 43.3% and 16.7%, respectively. The proliferation of MG-63 cells in RIPK4-siRNA group was lower than that in NC-siRNA group (P < 0.05). Furthermore, the proliferation in RIPK4-siRNA+TNF-a group was lower than those in other three groups (all P < 0.05). The apoptosis of MG-63 cells in RIPK4-siRNA groups was significantly higher than that in NC-siRNA group (P < 0.05). Furthermore, the apoptotic rate in RIPK4-siRNA+TNF-a group was significantly higher than those in other three groups (all P < 0.05). The expression levels of Bax and caspase-3 proteins in RIPK4-siRNA group were significantly higher than those in NC-siRNA group (P < 0.05), but the expression level of Bcl-xL protein in RIPK4-siRNA group was significantly lower than that in NC-siRNA group (P < 0.05). The expression levels of Bax and caspase-3 proteins in RIPK4-siRNA+TNF-a group were significantly increased, but the expression of Bcl-xL protein was significantly decreased as compared with other three groups (all P < 0.05). Conclusion: RIPK4 gene silencing can induce the apoptosis of MG-63 cells, and may increase the sensitivity of apoptosis induced by TNF-a.

Objective:To investigate the extracellular signal-regulated kinase 5 (ERK5) and matrix metallo proteinase-9 (MMP-9) expres-sion levels in osteosarcoma tissues and their clinical significance. Methods:The ERK5 and MMP-9 expression levels in 71 specimens of osteosarcoma tissue and 40 specimens of normal bone tissue were detected by immunohistochemistry. The relationship between ERK5 and MMP-9 expression levels, their clinical characteristics, and prognosis of patients with osteosarcoma were analyzed. Results:The positive expression of ERK5 and MMP-9 in osteosarcoma tissues was 85.9%(61/71) and 74.65%(53/71), respectively, which were significantly higher than those in normal bone tissues at 12.5%(5/40) and 10.0%(4/40) (all P<0.05). The positive expression of ERK5 and MMP-9 was associated with Enneking stage and metastasis (all P<0.05). Kaplan-Meier analysis showed that the survival duration of patients with positive ERK5 and MMP-9 expression levels was shorter than those of the patients in the negative expression groups (all P<0.05). Univariate analysis of COX proportional hazards regression model revealed that tumor size, Enneking stage, metastasis, and positive ERK5 and MMP-9 expression levels are relevant to the overall survival of patients with osteosarcoma (all P<0.05). Multi-variate analysis of COX proportional hazards regression model confirmed that Enneking stage, metastasis, and positive ERK5 and MMP-9 expression levels can act as independent prognostic factors for osteosarcoma patients (all P<0.05). Conclusion:The ERK5 and MMP-9 expression levels are high in osteosarcoma tissues and are related to the clinical characteristics and prognosis of patients with osteo-sarcoma. Thus, ERK5 and MMP-9 expression levels may play important roles in osteosarcoma development and progression.

AIM:To explore the time-dependent change of Ski protein expression in normal and activated astrocytes in rats.METHODS:The astrocytes were obtained from rat cerebral cortex and cultured in vitro.The astrocytes were treated with LPS and scratch injury for activation.Western blot analysis was used to determine glial fibrillary acidic protein (GFAP) and Ski protein levels in activated astrocytes at a series of time points.The indirect immunofluorescence staining method was performed to detect the location of Ski protein in the astrocytes.RESULTS:The protein of GFAP was naturally expressed in the astrocytes, beginning to increase after treated with LPS and scratch injury.Little protein expression of Ski in the normal astrocytes was observed.The Ski protein expression began to increase after treated with 1 mg/L LPS, peaked at 4 d (P<0.05) and then deceased, but was stills higher than that in the normal cells.The protein expression level of Ski after scratch injury was highly consistent with above mentioned.Ski was mainly observed in the nucleus of the normal cells and the cells treated with LPS for 6 d, while it was observed in the cytoplasm 2 and 4 d after treated with LPS.CONCLUSION:The protein of Ski is expressed in the astrocytes, and the expression level is increased in activated astrocytes,mainly located in the nucelus.Ski may plays an essential roles in the processes of activation and proliferation of astrocytes.