Comparative analysis of root anatomical structure, chemical components and differentially expressed genes between early bolting and unbolting in Peucedanum praeruptorum Dunn.

Early bolting of Peucedanum praeruptorum Dunn severely affects its quality. In this study, we compared with the root structure of P. praeruptorum and its four coumarins content between early bolting (CT) and unbolting (WT) at different growth stages. We found that the proportion of area outside the root cambium (Rs) was higher in the WT plants than in the CT plants and correlated positively with the proximity to the root tip. Furthermore, the content of all four coumarins was also higher in the WT plants relative to the CT plants. In addition, we identified 15,524 differentially expressed genes (DEGs) between the two plant varieties. 11 DEGs are involved in the photoperiod and gibberellin pathways that regulate early bolting and 24 genes involved in coumarins biosynthesis were also identified. Nevertheless, early bolting of P. praeruptorum does affect its quality formation, and further studies are needed to confirm its mechanism.

Machine learning-based rail corrugation recognition: a metro vehicle response and noise perspective.

Rail corrugation is a common problem in metro lines, and its efficient recognition is always an issue worth studying. To recognize the wavelength and amplitude of rail corrugation, a particle probabilistic neural network (PPNN) algorithm is developed. The PPNN is incorporated with the particle swarm optimization algorithm and the probabilistic neural network. On the basis of the above, the in-vehicle noise characteristics measured in the field are used to recognize normal rail wavelengths of 30 and 50 mm. A stepwise moving window search algorithm suitable for selecting features with a fixed order was developed to select in-vehicle noise features. Sound pressure levels at 400, 500, 630 and 800 Hz of in-vehicle noise are fed into the PPNN, and the average accuracy can reach 96.43%. The bogie acceleration characteristics calculated by the multi-body dynamics simulation model are used to recognize normal rail amplitudes of 0.1 and 0.2 mm. The bogie acceleration is decomposed by the complete ensemble empirical mode decomposition with adaptive noise, and a reconstructional signal is obtained. The energy entropy of the reconstructional signal is fed into the PPNN, and the average accuracy can reach 95.40%. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.

A novel smoothed (SMO) point mutation in congenital tibial hemimelia: a case report.

BACKGROUND: Congenital tibial hemimelia (CTH [MIM: 275220]) is a rare congenital limb deficiency that manifests as a shortened, curved, dysplastic or absent tibia with polydactyly. In previous studies, mutations of a distant sonic hedgehog (SHH) cis-regulator (ZRS) and a Shh repressor (GLI3) were identified. CASE PRESENTATION: Here, we admitted a 20-month-old boy who manifested with right tibial deformity, varus foot, ankle dislocation, and ipsilateral preaxial polydactyly. After genetic sequencing and data analysis, the results revealed a 443 A > G mutation in the father and a 536 C > T mutation in the mother in exon 2 of the Smoothed (SMO) gene at 7q32.1, with the coexistence of both mutant alleles in the proband/patient. CONCLUSIONS: Our report suggests that even though not previously reported, SMO mutations may be associated with limb anomalies such as tibial hemimelia via Hh signaling in humans and has implications for genetic counseling.

Treatment of Stage I-III Hip Joint Tuberculosis With Open Surgical Debridement and Hip Spica in Children: A Retrospective Study.

BACKGROUND: This study aimed to evaluate the outcome of surgical debridement combined with postoperative hip spica immobilization in the treatment of hip joint tuberculosis in children. METHODS: This retrospective study enrolled 87 children with stage I to III hip joint tuberculosis treated surgically at our hospital from January 2010 to January 2016. All patients considering hip tuberculosis routinely received a 4-week conservative treatment first, including rest, protected weight-bearing, and 4-drugs antitubercular chemotherapy. Surgical debridement was indicated when there was no relief after this conservative protocol. Patients were divided into 2 groups according to the duration of hip spica immobilization after operation: group A (hip spica for 4 wk, 39 patients) and group B (hip spica for 6 wk, 48 patients). All patients were recommended partial weight-bearing for 7 days and then followed the same hip joint exercises program when spica was removed. Postoperative radiographs, hip dislocation or subluxation, and modified Harris hip score (MHHS) were assessed. All patients were followed up at least 5 years. RESULTS: There were 87 patients enrolled in our study, including 34 females and 53 males, with a mean age of 7.2±2.8 years old (range: 2 to 14 y). No significant difference was observed between these 2 groups in baseline data. In group A, the mean MHHS improved from 52.1±14.7 before surgery to 87.8±8.3 at the final follow-up ( P <0.000). In group B, there was also a significant difference between the preoperative MHHS (52.7±9.4) and the final MHHS (88.6±6.5) ( P <0.000). Although there was no significant difference between these 2 groups in the final MHHS ( P =0.593), there were also no significant differences between these 2 groups in wound healing delay (3 in group A and 6 in group B, P =0.705) and pathologic subluxation (3 in group A and 1 in group B, P =0.467). The only difference between group A (79.2±8.5) and group B (75.5±7.5) was the early functional outcome assessed by using MHHS after 1 month of hip joint exercises ( P =0.032). CONCLUSIONS: Surgical debridement combined with antitubercular chemotherapy is an effective treatment for stage I to III hip tuberculosis in children when there is no improvement after conservative treatment. Prolonged hip spica immobilization may not reduce the risk of hip subluxation after open surgical debridement but could lead to a delay in early functional recovery. Time of spica immobilization should be individualized and based on the surgeon's evaluation and the patient's condition.

Polygonatum cyrtonema Hua Polysaccharides Protect BV2 Microglia Relief Oxidative Stress and Ferroptosis by Regulating NRF2/HO-1 Pathway.

Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases.

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

Cemented versus uncemented hemiarthroplasty for the management of femoral neck fractures in the elderly: a meta-analysis and systematic review.

INTRODUCTION: Hemiarthroplasty is commonly used to treat unstable femoral neck fractures in older patients. However, there is no consensus on the use of cement during hemiarthroplasty. Therefore, we performed a systematic review to focus on the outcomes of cemented and uncemented hemiarthroplasty for the treatment of femoral neck fractures in older patients. MATERIALS AND METHODS: Pubmed, Cochrane Central Register of Controlled Trials, and Ovid were searched for studies related comparison of cemented versus uncemented hemiarthroplasty for unstable femoral neck fractures from inception to Jan 20, 2020. The quality of the included randomized controlled trials (RCTs) was assessed using the Cochrane Collaboration tool. The meta-analysis was performed using the RevMan 5.2 software. RESULTS: Eleven RCTs were included in the meta-analysis. Cemented hemiarthroplasty was found to be superior to uncemented arthroplasty with respect to reoperation rate (RR 0.6, 95% CI 0.38-0.96, p = 0.03), complications related to prosthesis (RR 0.39, 95% CI 0.23-0.68, p = 0.0008), residual pain (RR 0.66, 95% CI 0.52-0.83, p = 0.0004), and operation time (MD 8.22, 95% CI 6.30-10.14, p < 0.00001). There were no significant between-group differences with respect to local and general complications, duration of hospital stay, hip function, and mortality. CONCLUSIONS: This meta-analysis showed cemented hemiarthroplasty might be an optimum choice for treating unstable femoral neck fractures in older patients. However, the results of this meta-analysis should be interpreted cautiously owing to some limitations. Further studies are required to provide more robust evidence.

[Research progress on anti-hyperuricemia effects and mechanisms of Chinese medicines based on regulation of intestinal flora and metabolites].

Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.

Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study.

Kaposiform hemangioendothelioma (KHE) is an aggressive disease with high morbidity and mortality. The aim of this study was to retrospectively evaluate the efficacy and safety of sirolimus for the treatment of progressive KHE. A multicenter, retrospective cohort study was conducted in patients with progressive KHE treated with sirolimus. A total of 52 patients were analyzed. Thirty-seven (71%) patients exhibited Kasabach-Merritt phenomenon (KMP) and were significantly younger than the patients without KMP [95% confidence interval (CI), 14.39-41.61; p < 0.001]. Patients without KMP were all treated with sirolimus alone, whereas 21 KMP patients with severe symptoms received short-term combination therapy with prednisolone. Overall, 96% and 98% of patients showed improved relief of notable symptoms and/or improved complications at 6 and 12 months after treatment, respectively. After sirolimus treatment, significant decreases in mean severity scores occurred at 6 months (95% CI, 2.23-2.54, p < 0.001) and 12 months (95% CI, 1.53-1.90, p < 0.001). Compared to KMP patients, patients without KMP showed a response that was similar to but less pronounced during the 12 months of treatment (95% CI, 40.87-53.80; p < 0.001). For subgroup analysis of KMP patients, there were no significant differences in tumor shrinkage between those treated with combination therapy and those receiving sirolimus alone (95% CI, 18.11-25.02; p > 0.05). No patients permanently discontinued treatment due to toxicity-related events, and no drug-related deaths occurred. Sirolimus was effective and safe for the treatment of progressive KHE. Sirolimus may be considered as a first-line therapy or as part of a multidisciplinary approach for the treatment of KHE.

[A case of skin autograft for skin ulcers in ichthyosis].

Ichthyosis refers to a group of skin diseases characterized by abnormal keratinization of the epidermis, resulting in dryness, roughness and scale of the skin. A girl with ichthyosis, who presented with skin ulcers and infection of the right dorsal foot, was admitted to our department. An autologous razor-thin skin grafting procedure was performed to repair the skin ulcers after debridement and vacuum sealing drain. After 8 months of follow-up, both the donor and recipient site healed well and there were no newly formed ulcers or infections. Although the skin quality of ichthyosis is poor, the lesion area can still be used as donor or recipient cite.

Analysis of risk factors for difficult implant removal in children with slipped capital femoral epiphysis treated by cannulated screws.

Introduction: Cannulated screws are widely used in the treatment of slipped capital femoral epiphysis, which can be removed after physeal closure on patient's request. This study aimed to analysis the potential risk factors for difficult removal in children with slipped capital femoral epiphysis treated by cannulated screws. Patients and methods: This study enrolled 32 hips that had undergone removal of cannulated screws after treatment of slipped capital femoral epiphysis at our department. The primary outcomes were the difficult screw removal. The secondary outcomes were functional outcome assessed by using a modified Harris Hip Score and complications of fractures and surgical site infection. Related risk factors for difficult removal were recorded and analyzed by multivariable logistic regression. Results: In total, 32 hips were evaluated, with a mean age of 14.9 ± 1.3 years old (range, 13-19 years). Six (18.8%) hips presented with difficult removal, including 4 cases of screws' slip and 2 breakages. The average implantation time in the difficult removal group (5.7 ± 1.0) was also significantly longer than that in the easily removed group (3.8 ± 0.9, p = 0.001). The mean surgical time in patients with difficult removal was 66.3 ± 11.6 min, which was also significantly longer than that (54.8 ± 8.3) in the other patients (p = 0.008). The duration of screw implantation was an independent risk factor for difficult removal. Conclusions: Prolonged screw duration was a predictor for difficult removal in children with slipped capital femoral epiphysis treated by cannulated screws. An early surgery after physeal closure might benefit those with a request for screw removal.

Pathological fracture increases the risk of unsatisfactory functional results and avascular necrosis in children with proximal femur simple bone cysts.

INTRODUCTION: Proximal femur simple bone cysts (SBCs) are rare in children, but with a risk of pathological fractures and the associated poor outcomes. This study aimed to evaluate the functional and radiographic outcomes of children with proximal femur SBCs. PATIENTS AND METHODS: 38 children with proximal femur SBCs treated surgically at our department, West China hospital, were enrolled in the study. Patients were divided into two groups according to whether pathological fractures presented before treatment. The non-fracture group received treatment of open curettage, cavity electrocauterization, bone grafting, and fixation (proximal femoral plate, intramedullary nail or Kirschner wire). The pathological fracture group received the same procedures of curettage, electrocauterization, grafting, and fixation. Autogenous iliac bone grafting was done in all cases, and the artificial bone was used as a supplementary based on the size of the cavity. Postoperatively, all patients underwent hip spica or similar orthosis immobilization for six weeks and received the same rehabilitation program after the removal of hip spica. Patients were evaluated by two independent observers, including the functional results based on the Ratliff's criteria, avascular necrosis, healing rate based on the Neer scoring system, coxa vara, and premature physeal arrest. We described the good outcome in Ratliff's criteria as "Satisfactory results", and fair and poor outcomes as "Unsatisfactory results." Grade 1 and grade 2 Neer results were termed as failures in treatment, and grades 3 and 4 were considered successes and healing. RESULTS: 38 patients with 38 hips (18 on the left side and 20 on the right side) were evaluated, including 9 females and 29 males, with a mean age of 9.0±2.6 years old (range, 5 to 14 years). There was no significant difference between these two groups in the baseline data of gender, age, side, grafting, staging, and fixation methods. The rate of unsatisfactory functional results in the pathological fractures group was 56.3% (9/16), significantly higher than that in patients without fracture (22.7%, 5/22. p= 0.047). There was also a significant difference in avascular necrosis of the femoral head between the pathological fractures group (7/16) and the group without fracture (2/22, p=0.021). Thirty cases presented with healing, including 13 in the fractures group and 17 in the non-fracture group (p=1.000), and eight cases were graded as failures (2 cases of grade 1 and 6 cases of grade 2). There were also no significant differences between these two groups in premature physeal arrest (2 in fracture group and 1 in non-fracture group, P=0.562), and Coxa vara (3 in the fracture group and 0 in non-fracture group, P=0.066). CONCLUSIONS: Pathological fracture significantly increases the risk of unsatisfactory functional results and avascular necrosis of the femoral head in patients with femoral neck SBCs. Prophylactic treatment and fixation of SBCs in weight bearing proximal femur region is better to manage without complications than managing with pathological fractures.

[Clinical characteristics of pediatric victims in the Lushan and Wenchuan earthquakes and experience of medical rescue].

OBJECTIVE: To get a more comprehensive understanding of the clinical characteristics of pediatric victims in earthquake and to summarize the experience of medical rescue. METHODS: The clinical information was collected from the pediatric victims who were admitted to West China Hospital, Sichuan University following the Lushan earthquake in 2013 and Wenchuan earthquake in 2008. The clinical data were compared between the pediatric victims in the two earthquakes. RESULTS: Thirty-four children under 14 years of age, who were injured in the Lushan earthquake, were admitted to the West China Hospital before April 30, 2013. Compared with the data in the Wenchuan earthquake, the mean age of the pediatric victims in the Lushan earthquake was significantly lower (P<0.01), and the mean time from earthquake to hospitalization was significantly shorter (P<0.01). In the Lushan earthquake, 67.6% of the injured children had variable limb fractures; traumatic brain injury was found in 29.4% of hospitalized children, versus 9.5% in the Wenchuan earthquake (P<0.05). Among the 34 children, no amputation and death occurred, and all the 13 severe cases started to recover. CONCLUSIONS: There were higher proportions of severely injured children and children with traumatic brain injury in the Lushan earthquake than in the Wenchuan earthquake. But these cases recovered well, which was possibly due to timely on-site rescue and transfer and multi-sector, multi-institution, and multidisciplinary cooperation.

Predictive factors for open reduction of operatively treated radial neck fractures in children.

INTRODUCTION: Open reduction is a therapeutic option for displaced radial neck fracture in children, which once was considered the last resort because of its potential risk for functional outcomes. This study aimed to identify risk factors for open reduction in operatively treated radial neck fractures in children. PATIENTS AND METHODS: One hundred and thirty-seven patients with displaced radial neck fractures, treated surgically at our department from January 2010 to December 2021 were retrospectively enrolled. Patients' data of age, sex, injury side, obesity, type of fractures, combined fractures, nerve injury, reduction methods, and delay from injury to surgery were reviewed. Univariate analysis and multivariate logistic regression were used to identify independent risk factors and odds ratios of open reduction. RESULTS: Overall, 137 patients (62 females and 75 males) with an average of 8.0 ± 2.2 years were analyzed. There were 62 cases of type III fractures and 75 cases of type IV based on the Judet classification. Thirty-two cases had combined fractures and 19 cases presented with nerve injury. The open reduction rate was 24.1 % (33/137). Univariate analysis indicated obesity, fracture type, and combined fractures were significantly associated with open reduction. (P = 0.039, P = 0.000 and P = 0.000, respectively). While multivariate logistic regression analysis showed that only fracture type (OR, 5.18; CI, 1.63-16.46, p = 0.005) and combined fractures (OR, 7.79; CI, 2.97-20.41, p = 0.000) were independent risk factors for open reduction. CONCLUSIONS: Judet type IV fracture and combined fractures are two significant risk factors for open reduction in operatively treated radial neck fractures in children. These findings will facilitate preoperative decision making, remind surgeons of the risk of failure in closed reduction and the use of new surgical techniques to decrease the open reduction poor outcome rate.

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review.

Background and Objective: Denosumab is a valuable and safe therapy for skeletal disorders in adults and has received regulatory approval to treat osteoporosis and bone metastases. However, denosumab is not licensed for pediatric use due to a lack of high-quality prospective research on children. This study aimed to describe and discuss the benefits and disadvantages of denosumab in treating bone diseases in children and to summarize the current understanding of the role of denosumab therapy in children. Methods: A narrative review was conducted using the literature retrieved from the PubMed, Embase, and Cochrane Library databases. Key Content and Findings: In children with type 6 osteogenesis imperfecta (OI), juvenile Paget disease (JPD), and secondary osteoporosis who show poor response to bisphosphonate, the use of denosumab has been reported to improve osteoporosis and increase bone mineral density (BMD). Moreover, for those with relapse, progressive and refractory aneurysmal bone cyst (ABC), fibrous dysplasia (FD), giant cell tumor of bone (GCTB), and central giant cell granuloma (CGCG) lesions, denosumab can improve pain symptoms, control disease progression, and reduce serious adverse events. Although there have been sporadic reports of adverse events such as hypocalcemia during medication and rebound hypercalcemia after discontinuation, early prevention, monitoring, and timely intervention can prevent children from experiencing severe adverse events. Conclusions: The published data indicate that denosumab has efficacy in alleviating disease in multiple refractory bone lesions in children.

Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

The outcome of loose bone fragments in pediatric supracondylar humerus fractures: a retrospective study.

We evaluated the clinical and imaging outcomes of loose bone fragments in children with supracondylar humerus fractures after closed reduction with percutaneous pin (CRPP) fixation. A retrospective review was conducted on 12 children with fragments on imaging after closed reduction of displaced humeral supracondylar fractures (Gartland III). Primary radiographic assessment included fragment outcome, postoperative Baumann angle, carrying angle and loss of reduction. Clinical outcome included the elbow range of motion (ROM), Flynn grade and other complications. Between January 2015 and January 2018, 460 children (2-14 years old) with supracondylar humerus fractures were treated at our center, including 12 (2.6%) with loose bone fragments on postoperative X-ray. Union or absorption of fragments was noted in all 12 patients at 1 year postoperatively, with good radiographic and clinical outcomes. The mean Baumann angle was 15.5° ± 4.3° and the mean carrying angle was 11.2° ± 2.8°. All patients had a normal elbow ROM. Ten patients achieved an excellent and two a good result according to the Flynn criteria. Good results were achieved after CRPP fixation in 12 children with supracondylar humerus fractures and loose bone fragments. The fragments were mainly absorbed or achieved union to the humerus within 1 year.