Objective To investigate the effect of treatment of avascular necrosis of femoral head in adolescence by implanting a composite of autogenous bone marrow, bone morphogenetic protein(BMP), and noncelluar tissue engineered bone allograft. Methods The BMP was partially purified from bovine cortical bone (bBMP) by Urist method. The bone allograft chips were mixed with bBMP and bone marrow. The composite was implanted into the necrotic area of the femoral head after core decompression, then partial deminerallized allograft fibula segments were inserted in the core decompression holes to support the necrotic area in preventing the collapse in 64 adolescent patients (78 hips). Results 55 cases (67 hips) were followed up for 3 months to 6 years(mean 44 months). 28 case(36 hips) in FicatⅠ,Ⅱ were followed up over 3 years, of whom there were no obvious pain and dysfunction in 18 cases(22 hips), high density new bone was shown in core decompression area in CT scanning, and no evidence of progressive necrosis. There was no worsening of the symptoms in 4 cases(6 hips) in Ficat Ⅰand Ⅱ, but the lesion progressed. In 6 cases (8 hips) in Ficat Ⅲ, there were no obvious pain and dysfunction in 2 cases, but 4 cases underwent total hip replacement because of persistent pain and progressive lesion. Conclusion The partial demineralized allograft fibula can provide direct mechanical support to prevent the necrotic femoral head from progress and collapse, autogenous bone marrow and BMP is able to promote new bone formation. The method can be used as an alternative for the treatment of osteonecrosis of femoral head at stage Ⅰ,Ⅱ.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative patient-controlled intravenous analgesia in pediatric patients undergoing lower extremity orthopedic surgery.Methods:Sixty-eight pediatric patients of both sexes, aged 3-15 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, undergoing elective lower extremity orthopedic surgery under general anesthesia, were divided into 2 groups ( n=34 each) by the random number table method: TEAS group (group T) and control group (group C). In group T, the bilateral Hegu and Neiguan acupoints were stimulated starting from 10 min before induction of anesthesia until the end of procedure, with the frequency of disperse-dense wave of 2/10 Hz, and the current intensity was gradually adjusted to the maximum intensity (10-15 mA) that children could tolerate. In group C, the electrodes were applied to the same acupoints, but electrical stimulation was not applied. The severity of pain was assessed by the Faces Pain Scale-Revised scale immediately after returning to the ward and at 2, 24 and 48 h after operation. The emergence agitation was evaluated using the Pediatric Anesthesia Emergence Delirium scale. The intraoperative consumption of propofol and remifentanil and time to extubation after stopping administration were recorded. The time to first pressing of patient-controlled analgesia (PCA), effective pressing times of PCA on 1st and 2nd days after surgery and postoperative adverse reactions such as postoperative nausea and vomiting, pruritus, drowsiness, and respiratory depression were recorded. Results:Compared with group C, the Faces Pain Scale-Revised scale scores were significantly decreased immediately after returning to the ward and at 2, 24 and 48 h after operation, the incidence of emergence agitation and intraoperative consumption of remifentanil were decreased, the time to extubation was shortened, the time to first pressing of PCA was prolonged, and the effective pressing times of PCA on 1st and 2nd days after surgery were decreased ( P<0.05). There was no significant difference in the intraoperative consumption of propofol and incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:TEAS can effectively enhance the effect of postoperative patient-controlled intravenous analgesia in pediatric patients undergoing lower extremity orthopedic surgery.

Objective:To investigate the role of methylation status of glutathione transferase mu5 (GSTM5) promoter region in the occurrence and development of myelodysplastic syndrome (MDS) and provide a new potential molecular marker for the early diagnosis of MDS.Method:Bone marrow blood samples were collected from 40 patients with initial diagnosis of MDS [5 cases of MDS with single dysplasia (MDS-SLD), 7 cases of MDS with multilineage dysplasia (MDS-MLD), 6 cases of MDS with ringed sideroblasts (MDS-RS), 13 patients with refractory with excess blast-1 (RAEB1), 9 patients with refractory with excess blast-2 (RAEB2)], 8 patients with AML secondary to MDS and 6 patients with non-malignant blood diseases(4 patients with iron deficiency anemia and 2 patients with nutritional megaloblastic anemia) in PLA General Hospital from October 2018 to June 2021. Methylation status of the promoter region of GSTM5 gene in three groups were detected by the Agena MassArray nucleic acid mass spectrometry. The Wilcoxon nonparametric test (non-normally distributed data, median (IQR)] was used to compare the methylation levels of GSTM5 gene in different groups. Receiver operating characteristic (ROC) curve was used to evaluate the specificity, sensitivity and accuracy of the test.Results:Cluster analysis showed that the methylation status of GSTM5 in MDS group was higher than that in control group [0.50 (0.27, 0.79) vs.0.29(0.10, 0.45), P<0.05]; The methylation status of GSTM5 in sAML group was significantly higher than that in MDS group [0.67 (0.36, 0.86) vs. 0.50 (0.27, 0.79), P<0.05].The differences in the methylation status of each CpG site were analyzed, and there were statistically significant differences between the MDS group and the control group at CpG_1, CpG_4, 5, CpG_6, 7, 8, CpG_11, CpG_13, 14, CpG_15, CpG_16, CpG_22 and CpG_24 sites ( P<0.05). The results of ROC curve analysis showed that the area under the CpG_6, 7, 8 site curves was the largest, with AUC=0.861(95% CI 0.717-1.000; P<0.05), and the sensitivity and specificity were 85% and 83%, respectively. By analyzing the relationship between GSTM5 methylation and MDS disease development, GSTM5 methylation levels were significantly increased in the higher bone marrow blast group and the high-risk subgroup (RAEB). Conclusion:Aberrant DNA promoter methylation of GSTM5 was a frequent event in MDS and may play an important role in the occurrence and development of MDS. It might be served as a promising biomarker in the diagnosis of MDS.

The association of Zika virus (ZIKV) infection with microcephaly has raised alarm worldwide. Their causal link has been confirmed in different animal models infected by ZIKV. However, the molecular mechanisms underlying ZIKV pathogenesis are far from clear. Hence, we performed global gene expression analysis of ZIKV-infected mouse brains to unveil the biolog-ical and molecular networks underpinning microcephaly. We found significant dysregulation of the sub-networks associated with brain development, immune response, cell death, microglial cell acti-vation, and autophagy amongst others. We provided detailed analysis of the related complicated gene networks and the links between them. Additionally, we analyzed the signaling pathways that were likely to be involved. This report provides systemic insights into not only the pathogenesis, but also a path to the development of prophylactic and therapeutic strategies against ZIKV infection.

Objective:To analyze the incidence of stillbirth and the associated factors in pregnancy among pregnant residents in Wuhan.Methods:A previous birth cohort was retrospectively reviewed. The cohort was based on Wuhan Maternal and Child Information System, and the perinatal information of pregnant residents in Wuhan from January 1, 2011, to September 30, 2017 and information of selected cases was collected, including socio-demographic characteristics, pregnant history, and healthcare information during pregnancy and labor. Data on stillbirth, including fetal death in uterus and in labor, were selected for this study. Chi-square test was adopted for comparing the differences in pregnancy-related factors between live birth and stillbirth, and binary logistic regressions for exploring the influencing factors associated with the occurrence of stillbirth. Results:A total of 509 057 deliveries in Wuhan were included in this study, including 505 839 live births and 3 218 stillbirths (3 155 after exclusion of fetal death in labor), with an overall incidence of stillbirth of 6.32‰(3 218/509 057), and an annual incidence between 4.90‰ to 8.11‰. Statistically significant differences were found between the live birth and stillbirth group in the following items: maternal age [<25 years old: 19.28% (97 544/505 839) vs 19.36% (623/3 218); 25-30 years old: 48.45% (245 077/505 839) vs 45.15% (1 453/3 218); 30-35 years old: 26.09% (131 952/505 839) vs 26.29% (846/3 218); >35 years old: 6.18% (31 266/505 839) vs 9.20% (296/3 218)], educational background [middle school or below: 22.90% (115 833/505 839) vs 22.03% (709/3 218); high school: 36.37% (183 978/505 839) vs 38.72% (1 246/3 218); college or above: 40.73% (206 028/505 839) vs 39.25% (1 263/3 218)], occupation [brainworker or professionals: 33.51% (169 514/505 839) vs 31.54% (1 015/3 218); manual or freelance worker: 66.38% (335 763/505 839) vs 68.34% (2 199/3 218)], residential area [urban area: 70.00% (354 365/505 839) vs 76.32% (2 456/3 218); rural area: 30.00% (151 474/505 839) vs 23.68%(762/3 218)], and time of conception [spring (March to May): 24.27% (122 746/505 839) vs 24.08% (775/3 218); summer (June to August): 24.09% (121 867/505 839) vs 23.87% (768/3 218); fall (September to November): 26.69% (135 012/505 839) vs 25.08% (807/3 218); winter (December to next February): 24.95% (126 214/505 839) vs 26.97% (868/3 218)] (all P<0.05), but no significant difference was found in fetal gender ( P>0.05). Besides, gravidity [once: 49.32% (249 484/505 839) vs 47.02% (1 513/3 218); over twice: 50.68% (256 355/505 839) vs 52.98% (1 705/3 218)], parity [once: 73.60% (372 316/505 839) vs 77.07% (2 480/3 218); over twice: 26.40% (133 523/505 839) vs 22.93% (738/3 218)], history of stillbirth [0.33% (842/256 355) vs 0.65% (11/1 705)], hypertensive disorders in pregnancy [3.25% (16 464/505 839) vs 5.59% (180/3 218)], first trimester vaginal bleeding [2.02% (10 251/505 839) vs 2.61% (84/3 218)], placenta previa [0.98% (4 963/505 491) vs 2.64% (53/2 009)], and oligohydramnios [2.52% (12 764/505 839) vs 1.90% (61/3 218)] differed significantly between the two groups (all P<0.05). However, no significant difference was found between the two groups in terms of the proportion of women with gestational diabetes mellitus and previous spontaneous abortion (both P>0.05). After exclusion of fetal death in labor from the 3 218 stillbirths, the same results were achieved. Binary logistic regression analysis showed that women who were over 30 years old (30-35 years old: OR=1.42, 95% CI: 1.30-1.56; >35 years old: OR=2.59, 95% CI: 2.25-2.98), with a high school degree or below (middle school or below: OR=1.37, 95% CI: 1.21-1.55; high school: OR=1.28, 95% CI: 1.16-1.42), manual or freelance worker ( OR=1.18, 95% CI: 1.07-1.31), in the urban area ( OR=1.43, 95% CI:1.31-1.57), and gravidity ≥ 2 times ( OR=1.32, 95% CI: 1.21-1.43), primiparity ( OR=1.76, 95% CI: 1.58-1.96), gestational hypertension ( OR=2.80, 95% CI: 2.40-3.27), vaginal bleeding in the first trimester ( OR=1.35, 95% CI: 1.08-1.68), placenta previa ( OR=10.86, 95% CI: 8.84-13.35) and history of stillbirth ( OR=2.27, 95% CI: 1.30-3.98) were all risk factors of stillbirth. Conclusion:Pregnant women who were over 30 years old, less educated, manual worker or freelance or with a history of adverse pregnancy, vaginal bleeding in the first trimester, hypertension in pregnancy, and placenta previa are at higher risk of stillbirth

Therapeutic nanoparticles are designed to enhance efficacy, real-time monitoring, targeting accuracy, biocompatibility, biodegradability, safety, and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials. Recently, bio-inspired metal nanoclusters (NCs) consisting of several to roughly dozens of atoms (<2 nm) have attracted increasing research interest, owing to their ultrafine size, tunable fluorescent capability, good biocompatibility, variable metallic composition, and extensive surface bio-functionalization. Hybrid core-shell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules, such as proteins (enzymes, antigens, and antibodies), DNA, and specific cells, create fluorescently visualized molecular nanoparticle. The resultant nanoparticles possess combinatorial properties and synergistic efficacy, such as simplicity, active bio-responsiveness, improved applicability, and low cost, for combination therapy, such as accurate targeting, bioimaging, and enhanced therapeutic and biocatalytic effects. In contrast to larger nanoparticles, bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems. Notably, advances in nanoscience, interfacial chemistry, and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes. The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications, with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds. In the different hybrid platform, we summarize the current challenges and emerging perspectives, which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.